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  • 1. Adolfsson, Jan
    et al.
    Garmo, Hans
    Varenhorst, Eberhard
    Ahlgren, Göran
    Ahlstrand, Christer
    Andren, Ove
    Örebro University, School of Health and Medical Sciences.
    Bill-Axelson, Anna
    Bratt, Ola
    Damber, Jan-Erik
    Hellström, Karin
    Hellström, Magnus
    Holmberg, Erik
    Holmberg, Lars
    Hugosson, Jonas
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Petterson, Bill
    Törnblom, Magnus
    Widmark, Anders
    Stattin, Pär
    Clinical characteristics and primary treatment of prostate cancer in Sweden between 1996 and 2005: Data from the national prostate cancer register in Sweden2007In: Scandinavian Journal of Urology and Nephrology, ISSN 0036-5599, E-ISSN 1651-2065, Vol. 41, no 6, p. 456-477Article in journal (Refereed)
    Abstract [en]

    Objective. The incidence of prostate cancer is rising rapidly in Sweden and there is a need to better understand the pattern of diagnosis, tumor characteristics and treatment. Material and methods. Between 1996 and 2005, all new cases of adenocarcinoma of the prostate gland were intended to be registered in the National Prostate Cancer Register (NPCR). This register contains information on diagnosing unit, date of diagnosis, cause of diagnosis, tumor grade, tumor stage according to the TNM classification in force, serum prostate-specific antigen (PSA) levels at diagnosis and primary treatment given within the first 6 months after diagnosis. Results. In total, 72 028 patients were registered, comprising >97% of all pertinent incident cases of prostate cancer in the Swedish Cancer Register (SCR). During the study period there was a considerable decrease in median age at the time of diagnosis, a stage migration towards smaller tumors, a decrease in median serum PSA values at diagnosis, a decrease in the age-standardized incidence rate of men diagnosed with distant metastases or with a PSA level of >100 ng/ml at diagnosis and an increase in the proportion of tumors with Gleason score ≤6. Relatively large geographical differences in the median age at diagnosis and the age-standardized incidence of cases with category T1c tumors were observed. Treatment with curative intent increased dramatically and treatment patterns varied according to geographical region. In men with localized tumors and a PSA level of <20 ng/ml at diagnosis, expectant treatment was more commonly used in those aged ≥75 years than in those aged <75 years. Also, the pattern of endocrine treatment varied in different parts of Sweden. Conclusions. All changes in the register seen over time are consistent with increased diagnostic activity, especially PSA testing, resulting in an increased number of cases with early disease, predominantly tumors in category T1c. The patterns of diagnosis and treatment of prostate cancer vary considerably in different parts of Sweden. The NPCR continues to be an important source for research, epidemiological surveillance of the incidence, diagnosis and treatment of prostate cancer

  • 2.
    Ahl, R.
    et al.
    Department of Surgery, Karolinska University Hospital, Stockholm, Sweden; School of Medical Sciences, Örebro University, Örebro, Sweden.
    Matthiessen, P.
    School of Medical Sciences, Örebro University, Örebro, Sweden; Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Fang, X.
    Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Cao, Yang
    Örebro University, School of Medical Sciences. Örebro University Hospital. Unit of Biostatistics, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; .
    Sjölin, Gabriel
    Örebro University, School of Medical Sciences. Department of Surgery.
    Lindgren, R.
    Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Mohseni, Shahin
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Surgery.
    Effect of beta-blocker therapy on early mortality after emergency colonic cancer surgery2018In: British Journal of Surgery, ISSN 0007-1323, E-ISSN 1365-2168Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Emergency colorectal cancer surgery is associated with significant mortality. Induced adrenergic hyperactivity is thought to be an important contributor. Downregulating the effects of circulating catecholamines may reduce the risk of adverse outcomes. This study assessed whether regular preoperative beta-blockade reduced mortality after emergency colonic cancer surgery.

    METHODS: This cohort study used the prospectively collected Swedish Colorectal Cancer Registry to recruit all adult patients requiring emergency colonic cancer surgery between 2011 and 2016. Patients were subdivided into those receiving regular beta-blocker therapy before surgery and those who were not (control). Demographics and clinical outcomes were compared. Risk factors for 30-day mortality were evaluated using Poisson regression analysis.

    RESULTS: A total of 3187 patients were included, of whom 685 (21·5 per cent) used regular beta-blocker therapy before surgery. The overall 30-day mortality rate was significantly reduced in the beta-blocker group compared with controls: 3·1 (95 per cent c.i. 1·9 to 4·7) versus 8·6 (7·6 to 9·8) per cent respectively (P < 0·001). Beta-blocker therapy was the only modifiable protective factor identified in multivariable analysis of 30-day all-cause mortality (incidence rate ratio 0·31, 95 per cent c.i. 0·20 to 0·47; P < 0·001) and was associated with a significant reduction in death of cardiovascular, respiratory, sepsis and multiple organ failure origin.

    CONCLUSION: Preoperative beta-blocker therapy may be associated with a reduction in 30-day mortality following emergency colonic cancer surgery.

  • 3.
    Ahmad, Abrar
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Askari, Shlear
    Department of Clinical Medicine, Örebro University, Örebro, Sweden.
    Befekadu, Rahel
    Örebro University Hospital. Department of Laboratory Medicine, Section for Transfusion Medicine.
    Hahn-Strömberg, Victoria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Investigating the association between polymorphisms in connective tissue growth factor and susceptibility to colon carcinoma2015In: Molecular Medicine Reports, ISSN 1791-2997, E-ISSN 1791-3004, Vol. 11, no 4, p. 2493-2503Article in journal (Refereed)
    Abstract [en]

    There have been numerous studies on the gene expression of connective tissue growth factor (CTGF) in colorectal cancer, however very few have investigated polymorphisms in this gene. The present study aimed to determine whether single nucleotide polymorphisms (SNPs) in the CTGF gene are associated with a higher susceptibility to colon cancer and/or an invasive tumor growth pattern. The CTGF gene was genotyped for seven SNPs (rs6918698, rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) by pyrosequencing. Formalin-fixed paraffin-embedded tissue samples (n=112) from patients diagnosed with colon carcinoma, and an equal number of blood samples from healthy controls, were selected for genomic DNA extraction. The complexity index was measured using images of tumor samples (n=64) stained for cytokeratin-8. The images were analyzed and correlated with the identified CTGF SNPs and clinicopathological parameters of the patients, including age, gender, tumor penetration, lymph node metastasis, systemic metastasis, differentiation and localization of tumor. It was demonstrated that the frequency of the SNP rs6918698 GG genotype was significantly associated (P=0.05) with an increased risk of colon cancer, as compared with the GC and CC genotypes. The other six SNPs (rs1931002, rs9493150, rs12526196, rs12527705, rs9399005 and rs12527379) exhibited no significant difference in the genotype and allele frequencies between patients diagnosed with colon carcinoma and the normal healthy population. A trend was observed between genotype variation at rs6918698 and the complexity index (P=0.052). The complexity index and genotypes for any of the studied SNPs were not significantly correlated with clinical or pathological parameters of the patients. These results indicate that the rs6918698 GG genotype is associated with an increased risk of developing colon carcinoma, and genetic variations at the rs6918698 are associated with the growth pattern of the tumor. The present results may facilitate the identification of potential biomarkers of the disease in addition to drug targets.

  • 4.
    Ahmad, Abrar
    et al.
    Örebro University Hospital. Department of Clinical Research, Örebro University Hospital, Örebro, Sweden.
    Venizelos, Nikolaos
    Department of Clinical Research, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Hahn-Strömberg, Victoria
    Örebro University Hospital. Department of Clinical Research, Örebro University Hospital, Örebro, Sweden; ; Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
    Prognostic Effect of Vascular Endothelial Growth Factor +936C/T Polymorphism on Tumor Growth Pattern and Survival in Patients Diagnosed with Colon Carcinoma2016In: Journal of Tumor Research, Vol. 2, no 1, p. 1-6, article id 1000108Article in journal (Refereed)
    Abstract [en]

    Introduction: Vascular endothelial growth factor (VEGF) is considered as endothelial cell-specific mitogen that plays an important role in the process of angiogenesis, thereby affecting the prognosis of tumor as angiogenesis is a crucial phase in tumor growth and metastasis. Accordingly, we carried out a case-control study to assess whether VEGF rs3025039 polymorphism affects the growth pattern and susceptibility to colon carcinoma.

    Materials and methods: One hundred and fifty, formalin fixed paraffin embedded (FFPE) tissue samples from patients diagnosed with colon carcinoma and the same number of blood controls were used in the present study. VEGF +936 C>T (rs3025039) polymorphism was evaluated by pyrosequencing. Computer image analysis was used to analyse the growth pattern of the colon carcinoma tumor by using cytokeratin-8 stained slides.

    Results: A heterozygous genotype TC in rs3025039 polymorphism was found as a significantly protective genotype as compared to homozygous genotypes (CC and TT). However we found no significant correlation between investigated polymorphisms, tumor growth pattern, 5 years survival and other clinicopathological parameters.

    Conclusion: We concluded that the heterogenous genotype of VEGF rs3025039 polymorphism appears to be a protective factor for colon carcinoma that could be a useful marker in follow-up studies and may be a genetic determinant for colon carcinoma.

  • 5.
    Akre [Fall], Katja
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Ekström, A. M.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Signorello, L B
    2International Epidemiology Institute, Rockville, USA.
    Hansson, L.-E.
    Mora Hospital, Mora.
    Nyrén, O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm.
    Aspirin and risk for gastric cancer: a population-based case-control study in Sweden2001In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 84, no 7, p. 965-8Article in journal (Refereed)
    Abstract [en]

    While aspirin and other non-steroid anti-inflammatory drugs (NSAIDs) are associated with gastric mucosal damage, they might reduce the risk for gastric cancer. In a population-based case-control study in 5 Swedish counties, we interviewed 567 incident cases of gastric cancer and 1165 controls about their use of pain relievers. The cases were uniformly classified to subsite (cardia/non-cardia) and histological type and information collected on other known risk factors for gastric cancer. Helicobacter pylori serology was tested in a subset of 542 individuals. Users of aspirin had a moderately reduced risk of gastric cancer compared to never users; odds ratio (OR) adjusted for age, gender and socioeconomic status was 0.7 (95% CI = 0.6-1.0). Gastric cancer risk fell with increasing frequency of aspirin use (P for trend = 0.02). The risk reduction was apparent for both cardia and non-cardia tumours but was uncertain for the diffuse histologic type. No clear association was observed between gastric cancer risk and non-aspirin NSAIDs or other studied pain relievers. Our finding lends support to the hypothesis that use of aspirin reduces the risk for gastric cancer.

  • 6.
    Akre [Fall], Katja
    et al.
    Department of Medical Epidemiology, Karolinska Institute, Stockholm.
    Signorello, Lisa B.
    Engstrand, Lars
    Bergström, Reinhold
    Larsson, Sune
    Eriksson, Bengt I.
    Nyrén, Olof
    Risk for gastric cancer after antibiotic prophylaxis in patients undergoing hip replacement2000In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 60, no 22, p. 6376-80Article in journal (Refereed)
    Abstract [en]

    Despite strong evidence of an association between Helicobacter pylori and gastric cancer, the benefit of eradicating H. pylori infection is unknown. Our aim was to test the hypothesis that exposure to high doses of antibiotics reduces risk for gastric cancer via possible eradication of H. pylori We conducted a nationwide case-control study nested in a cohort of 39,154 patients who underwent hip replacement surgery between 1965 and 1983. Such patients frequently receive prophylactic antibiotic treatment. During follow-up through 1989, we identified 189 incident cases of gastric cancer. For each case, three controls were selected from the cohort. Exposure data were abstracted from hospital records. Blood samples from a separate cohort undergoing hip replacement surgery were analyzed for anti-H. pylori IgG before and after surgery. Both long-term antibiotic treatment before surgery [odds ratio (OR), 0.3; 95% confidence interval (CI), 0.1-0.7] and prophylactic antibiotic treatment (OR, 0.7; 95% CI, 0.5-1.1) conferred a reduction in gastric cancer risk. The reduction appeared stronger after 5 years (OR, 0.6; 95% CI, 0.3-1.2) than during shorter follow-up after hip replacement (OR, 0.8; 95% CI, 0.4-1.7). There was an apparent decrease in risk with increasing body weight-adjusted doses of antibiotics (P = 0.13). However, the rate of H. pylori antibody disappearance was not strikingly higher in the cohort of patients undergoing hip replacement than in a control cohort. Our findings provide indirect support for the hypothesis that treatment with antibiotics at a relatively advanced age reduces the risk of gastric cancer.

  • 7.
    Albrow, Rebecca
    et al.
    Sch Canc & Enabling Sci, Univ Manchester, Manchester, England.
    Blomberg, Karin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Kitchener, Henry
    Sch Canc & Enabling Sci, Univ Manchester, Manchester, England.
    Brabin, Loretta
    Sch Canc & Enabling Sci, Univ Manchester, Manchester, England.
    Patnick, Julietta
    NHS Canc Screening Programmes, Sheffield, England.
    Tishelman, Carol
    Med Management Ctr, Dept Learning Informat Management & Eth, Karolinska Inst, Stockholm, Sweden.
    Törnberg, Sven
    Regional Cancer Center, Dept Cancer Screening, Stockholm, Sweden.
    Sparen, Par
    Dept Med Epidemiol & Biostat, Karolinska Inst, Stockholm, Sweden.
    Widmark, Catarina
    Med Management Ctr, Dept Learning Informat Management & Eth, Karolinska Inst, Stockholm, Sweden; Dept Qual & Patient Safety, Karolinska Univ Hosp, Stockholm, Sweden.
    Interventions to improve cervical cancer screening uptake amongst young women: A systematic review2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 4, p. 445-451Article, review/survey (Refereed)
    Abstract [en]

    Objectives. In view of declining screening uptake in young women, this review aims to summarise the available evidence relating to interventions designed to increase cervical screening uptake amongst women aged <= 35 years.

    Methods. Electronic databases were searched and further articles located by manual searches. Study designs employing a valid comparison group and including women aged <= 35 years published through 2012 were considered. Data was extracted on the uptake from either screening programme statistics or as reported by the study subjects. A narrative synthesis was undertaken for each category of interventions identified.

    Results. Ninety-two records were screened with 36 articles retrieved for further assessment. Four studies met the inclusion criteria, two of which evaluated more than one intervention. One of the studies evaluated the use of a modified invitation letter and reported no significant increase in uptake compared to a standard invitation. Three studies investigated the use of a reminder letter, with two reporting a positive effect on screening uptake in women aged 24-34. Three studies were included which supported the use of physician and telephone reminders. One study on HPV self-sampling reported a positive effect when compared with a reminder letter.

    Conclusions. There is a lack of randomised controlled trials designed to specifically address falling cervical screening uptake in amongst young women. Cervical screening programmes need to look beyond the use of invitation/reminders letters in this group of women to develop interventions which attempt to overcome as many barriers to uptake as possible.

  • 8.
    Alhamdow, Ayman
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Lindh, Christian
    Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Hagberg, Jessika
    Örebro University, School of Science and Technology. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Graff, Pål
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden; National Institute of Occupational Health, Oslo, Norway.
    Westberg, Håkan
    Örebro University, School of Science and Technology. Department of Occupational and Environmental Medicine, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Krais, Annette M.
    Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Albin, Maria
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden; Centre for Occupational and Environmental Medicine (CAMM), Stockholm County Council, Stockholm, Sweden.
    Gustavsson, Per
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Centre for Occupational and Environmental Medicine (CAMM), Stockholm County Council, Stockholm, Sweden.
    Tinnerberg, Håkan
    Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    Broberg, Karin
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden; Division of Occupational and Environmental Medicine, Department of Laboratory Medicine, Lund University, Lund, Sweden.
    DNA-methylation of the cancer-related genes F2RL3 and AHRR is associated with occupational exposure to polycyclic aromatic hydrocarbons2018In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 39, no 7, p. 869-878Article in journal (Refereed)
    Abstract [en]

    Some polycyclic aromatic hydrocarbons (PAH) are known carcinogens and workplace PAH exposure may increase the risk of cancer. Monitoring early cancer-related changes can indicate whether the exposure is carcinogenic. Here, we enrolled 151 chimney sweeps, 152 controls, and 19 creosote-exposed male workers from Sweden. We measured urinary PAH metabolites using LC/MS/MS, the cancer-related markers telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) using qPCR, and DNA methylation of lung cancer-related genes F2RL3 and AHRR using pyrosequencing. The median 1-hydroxypyrene (PAH metabolite) concentrations were highest in creosote-exposed workers (8.0 μg/g creatinine) followed by chimney sweeps (0.34 μg/g creatinine) and controls (0.05 μg/g creatinine). TL and mtDNAcn did not differ between study groups. Chimney sweeps and creosote-exposed workers had significantly lower methylation of AHRR CpG site cg05575921 (88.1% and 84.9%, respectively) than controls (90%). Creosote-exposed workers (73.3%), but not chimney sweeps (76.6%) had lower methylation of F2RL3 cg03636183 than controls (76.7%). Linear regression analyses showed that chimney sweeps had lower AHRR cg05575921 methylation (B=-2.04; P<0.057, adjusted for smoking and age) and lower average AHRR methylation (B=-2.05; P<0.035), and non-smoking chimney sweeps had lower average F2RL3 methylation (B=-0.81; P<0.042, adjusted for age) compared with controls. These cancer-related markers were not associated with urinary concentrations of PAH metabolites. In conclusion, although we found no associations with PAH metabolites in urine (short-term exposure), our results suggest dose-response relationship between PAH exposure and DNA hypomethylation of lung cancer-related loci. These findings indicate that further protective measures should be taken to reduce PAH exposure.

  • 9.
    Ali, Imran
    et al.
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Julin, Bettina
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Glynn, Anders
    The National Food Agency, Uppsala, Sweden.
    Högberg, Johan
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Berglund, Marika
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Johansson, Jan-Erik
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andersson, Swen-Olof
    School of Health and Medical Sciences, Örebro University, Örebro, Sweden; Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Giovannucci, Edward
    Department of Nutrition, Harvard T. H. Chan School of Public Health, Boston MA, United States; Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston MA, United States; Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston MA, United States.
    Wolk, Alicja
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Stenius, Ulla
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Åkesson, Agneta
    Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Exposure to polychlorinated biphenyls and prostate cancer: population-based prospective cohort and experimental studies2016In: Carcinogenesis, ISSN 0143-3334, E-ISSN 1460-2180, Vol. 37, no 12, p. 1144-1151Article in journal (Refereed)
    Abstract [en]

    Polychlorinated biphenyls (PCBs) are highly persistent environmental pollutants and are undesirable components of our daily food. PCBs are classified as human carcinogens, but the evidence for prostate cancer is limited and available data are inconsistent. We explored the link between non-dioxin-like PCB and grade of prostate cancer in a prospective cohort as well as in cell experiments. A population-based cohort of 32496 Swedish men aged 45-79 years was followed prospectively through 1998-2011, to assess the association between validated estimates of dietary PCB exposure and incidence of prostate cancer by grade (2789 cases, whereof 1276 low grade, 756 intermediate grade, 450 high grade) and prostate cancer mortality (357 fatal cases). In addition, we investigated a non-dioxin-like PCB153-induced cell invasion and related markers in normal prostate stem cells (WPE-stem) and in three different prostate cancer cell lines (PC3, DU145 and 22RV1) at exposure levels relevant to humans. After multivariable-adjustment, dietary PCB exposure was positively associated with high-grade prostate cancer, relative risk (RR) 1.35 [95% confidence interval (CI): 1.03-1.76] and with fatal prostate cancer, RR 1.43 (95% CI: 1.05-1.95), comparing the highest tertile with the lowest. We observed no association with low or intermediate grade of prostate cancer. Cell invasion and related markers, including MMP9, MMP2, Slug and Snail, were significantly increased in human prostate cancer cells as well as in prostate stem cells after exposure to PCB153. Our findings both from the observational and experimental studies suggest a role of non-dioxin-like PCB153 in the development of high-grade and fatal prostate cancer.

  • 10. Amundadottir, Laufey T.
    et al.
    Sulem, Patrick
    Gudmundsson, Julius
    Helgason, Agnar
    Baker, Adam
    Agnarsson, Bjarni A.
    Sigurdsson, Asgeir
    Benediktsdottir, Kristrun R.
    Cazier, Jean-Baptiste
    Sainz, Jesus
    Jakobsdottir, Margret
    Kostic, Jelena
    Magnusdottir, Droplaug N.
    Ghosh, Shyamali
    Agnarsson, Kari
    Birgisdottir, Birgitta
    Le Roux, Louise
    Olafsdottir, Adalheidur
    Blondal, Thorarinn
    Andresdottir, Margret
    Gretarsdottir, Olafia Svandis
    Bergthorsson, Jon T.
    Gudbjartsson, Daniel
    Gylfason, Arnaldur
    Thorleifsson, Gudmar
    Manolescu, Andrei
    Kristjansson, Kristleifur
    Geirsson, Gudmundur
    Isaksson, Helgi
    Douglas, Julie
    Johansson, Jan-Erik
    Örebro University, Department of Clinical Medicine.
    Bälter, Katarina
    Wiklund, Fredrik
    Montie, James E.
    Yu, Xiaoying
    Suarez, Brian K.
    Ober, Carole
    Cooney, Kathleen A.
    Gronberg, Henrik
    Catalona, William J.
    Einarsson, Gudmundur V.
    Barkardottir, Rosa B.
    Gulcher, Jeffrey R.
    Kong, Augustine
    Thorsteinsdottir, Unnur
    Stefansson, Kari
    A common variant associated with prostate cancer in European and African populations2006In: Nature Genetics, ISSN 1061-4036, E-ISSN 1546-1718, Vol. 38, no 6, p. 652-658Article in journal (Refereed)
    Abstract [en]

    With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.

  • 11.
    Andersen, Christen Lykkegaard
    et al.
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark..
    Bjorn, Mads Emil
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark..
    McMullin, Mary Frances
    Dept Haematol, Queen Univ Belfast Antrim, Belfast, North Ireland.
    Harrison, Claire
    Dept Haematol, NHS Fdn Trust, London, England.
    Samuelsson, Jan
    Dept Internal Med, Stockholm South Hosp, Stockholm, Sweden..
    Ejerblad, Elisabeth
    Dept Hematol, Univ Uppsala Hosp, Uppsala, Sweden..
    Zweegman, Sonja
    Dept Hematol, Vrije Univ Med Ctr, Amsterdam, Netherlands..
    Fernandes, Savio
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Bareford, David
    Dept Haematol, Russells Hall Hosp, Dudley, England.
    Knapper, Steven
    Dept Haematol, Cardiff Univ, Cardiff, UK.
    Lofvenberg, Eva
    Hematol Ctr, Karolinska Univ Hosp, Stockholm, Sweden.
    Linder, Olle
    Dept Med, Div Hematol, Örebro Univ Hosp, Örebro, Sweden..
    Andreasson, Bjorn
    Dept Hematol, NU Hosp Org, Uddevalla Hosp, Uddevalla, Sweden.
    Ahlstrand, Erik
    Örebro University Hospital. Dept Med, Div Hematol, Örebro University Hospital, Örebro, Sweden.
    Jensen, Morten Krogh
    Dept Hematol, Herlev Hosp, Herlev, Denmark.
    Bjerrum, Ole Weis
    Dept Hematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Vestergaard, Hanne
    Dept Hematol, Odense Univ Hosp, Odense, Denmark.
    Larsen, Herdis
    Dept Hematol, Dept Internal Med, Viborg Hosp, Viborg, Denmark.
    Klausen, Tobias Wirenfeldt
    Dept Hematol,Herlev Hosp, Herlev, Denmark.
    Mourits-Andersen, Torben
    Dept Hematol, Esbjerg Cent Hosp, Esbjerg, Denmark.
    Skov, Vibe
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Thomassen, Mads
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Kruse, Torben
    Dept Clin Genet, Odense Univ Hosp, Odense, Denmark.
    Gronbaek, Kirsten
    Dept Hematol, Copenhagen Univ Hosp, Rigshosp, Copenhagen, Denmark.
    Hasselbalch, Hans Carl
    Dept Hematol, Roskilde Univ Hosp, Roskilde, Denmark.
    Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat2014In: Leukemia research: a Forum for Studies on Leukemia and Normal Hemopoiesis, ISSN 0145-2126, E-ISSN 1873-5835, Vol. 38, no 7, p. 816-821Article in journal (Refereed)
    Abstract [en]

    YKL-40 regulates vascular endothelial growth factors and induces tumor proliferation. We investigated YKL-40 before and after treatment with vorinostat in 31 polycythemia vera (PV) and 16 essential thrombocythemia (ET) patients. Baseline PV patient levels were 2 times higher than in healthy controls (P<0.0001) and 1.7 times higher than in ET (P = 0.02). A significant correlation between YKL-40 at baseline and neutrophils, CRP, LDH, JAK2V617F and platelets in PV patients was observed, as well as a significantly greater reduction of YKL-40 levels in PV patients responding to therapy. YKL-40 might be a novel marker of disease burden and progression in myeloproliferative neoplasms.

  • 12.
    Andersson, Patiyan
    et al.
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Kolaric, Aleksandra
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    Windahl, Torgny
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Kirrander, Peter
    Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Söderkvist, Peter
    Division of Cell Biology, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
    Karlsson, Mats G
    Department of Pathology, Örebro University Hospital, Örebro, Sweden.
    PIK3CA, HRAS and KRAS gene mutations in human penile cancer2008In: Journal of Urology, ISSN 0022-5347, E-ISSN 1527-3792, Vol. 179, no 5, p. 2030-2034Article in journal (Refereed)
    Abstract [en]

    Purpose: The knowledge of somatic mutations that arise in penile cancer is limited. We examined the dysregulation of components in the phosphatidylinositol 3-kinase and Ras pathways.

    Materials and Methods: Using single stranded conformational analysis and direct sequencing we performed mutational analysis of the PIK3CA, PTEN, HRAS, KRAS, NRAS and BRAF genes in 28 penile tumors.

    Results: We identified somatic missense mutations in 11 of the 28 penile cancer samples (39%). In the PIK3CA gene 8 mutations (29%) were identified that were E542K or E545K. In the HRAS gene a G12S and a Q61L mutation were found (7%). The KRAS gene contained 1 mutation (3%), that is a G12S change. PIK3CA mutations were found in all grades and stages, whereas HRAS and KRAS mutations were found in larger and more advanced tumors. The mutations were mutually exclusive, suggesting that dysregulation of either pathway is sufficient for the development and progression of penile carcinoma.

    Conclusions: The high frequency of mutations in the PIK3CA, HRAS and KRAS genes leads us to believe that dysregulation of the phosphatidylinositol 3-kinase or Ras pathway is significant for the development and progression of penile carcinoma.

  • 13.
    Anderzen Carlsson, Agneta
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Leibring, Ingela
    Fear and coping during treatment for acute lymphatic leukemia: from the perspective of children 5-9 years old2018Conference paper (Refereed)
    Abstract [en]

    Background: The concept of fear can be defined as ”an unpleasant often strong emotion caused by expectation of danger”. It is reasonable to believe that fear and coping of fear, can vary during the course of treatment for ALL. The aim of the present study was to describe a longitudinal perspective on fear related to having ALL, based on children’s perspective, as well as to describe the strategies these children use when experiencing fear.

    Design: The study has a longitudinal descriptive qualitative design. Three girls and 10 boys, initially aged 5-9 were interviewed once to three times during their treatment period (approximately two months after the diagnosis, after one year and at the end of the 2.5-year long treatment). In total, 35 interviews were conducted. Data were analyzed using a matrix-based qualitative analysis method.

    Results: The children described fear of being subjected to needles and related to having a feeding tube, to remove adhesive tape and taking tablets, as well as fear related to the bodily changes caused by the ALL. Existential fears were most frequently mentioned at end of treatment. The children wanted to participate in their care. They used cognitive strategies, such as ”thinking the right way” and emotional strategies, such as crying out loud and kicking. The fears changed over time, but the fear of being subjected to needles remained for half of the children, but was less intense at the end of treatment. The strategies developed, and became more sophisticated over the treatment period.

    Conclusion: The fear changed throughout the course of treatment, and so did the strategies used. It is reasonable to believe that the need for support also vary, which is a topic for future research.

  • 14.
    Anderzen-Carlsson, Agneta
    et al.
    Örebro University, School of Health Sciences. Örebro University Hospital.
    Leibring, I.
    Karlstad University, Faculty of Health- Science and Technology- Department of Health Sciences- Nursing, Karlstad, Sweden.
    Fear and Coping During Treatment for Acute Lymphatic Leukemia - from the Perspective of Children 5-9 Years Old2018In: Pediatric Blood & Cancer, ISSN 1545-5009, E-ISSN 1545-5017, Vol. 65, no Suppl.2, p. S598-S598Article in journal (Other academic)
    Abstract [en]

    Background/Objectives: The concept of fear can be defined as ”an unpleasant often strong emotion caused by expectation of danger”. It is reasonable to believe that fear and coping of fear, can vary during the course of treatment for ALL. The aim of the present study was to describe a longitudinal perspective on fear related to having ALL, based on children's perspective, as well as to describe the strategies these children use when experiencing fear.

    Design/Methods: The study has a longitudinal descriptive qualitative design. Three girls and 10 boys, initially aged 5-9 were interviewed once to three times during their treatment period (approximately two months after the diagnosis, after one year and at the end of the 2.5-year long treatment). In total, 35 interviews were conducted. Data were analyzed using a matrix-based qualitative analysis method.

    Results: The children described fear of being subjected to needles and related to having a feeding tube, removing adhesive tape and taking tablets, as well as fear related to the bodily changes caused by the ALL. Existential fears were most frequently mentioned at the end of treatment. The children wanted to participate i n their care. They used cognitive strategies, such as ”thinking the right way” and emotional strategies, such as crying out loud and kicking. The fears changed over time, but the fear of being subjected to needles remained for half of the children, but was less intense at the end of treatment. The strategies developed, and became more sophisticated over the treatment period.

    Conclusions: The fear changed throughout the course of treatment, and so did the strategies used. It is reasonable to believe that the need for support also vary, which i s a topic for future research.

  • 15.
    Anderzén-Carlsson, Agneta
    Örebro University, School of Health and Medical Sciences.
    Aktuell forskare om barn med cancer, deras rädsla och sättet den hanteras på2008In: Barnbladet, ISSN 0349-1994, Vol. 33, no 2, p. 45-46Article in journal (Other (popular science, discussion, etc.))
  • 16.
    Anderzén-Carlsson, Agneta
    Örebro University, School of Health and Medical Sciences.
    Att hantera rädsla hos barn med cancer2008In: Onkologi i Sverige, ISSN 1653-1582, Vol. 4, no 6, p. 14-20Article in journal (Other (popular science, discussion, etc.))
  • 17.
    Anderzén-Carlsson, Agneta
    Örebro University, Department of Health Sciences.
    Existentiella rädslor hos barn med cancer: föräldrars och vårdpersonals berättelser2007In: Omsorg: Nordisk tidsskrift for Palliativ Medisin, ISSN 0800-7489, Vol. 24, no 4, p. 33-39Article in journal (Other academic)
  • 18.
    Anderzén-Carlsson, Agneta
    et al.
    Örebro University, School of Health and Medical Sciences.
    Kihlgren, Annica
    Örebro University, School of Health and Medical Sciences.
    Sörlie, Venke
    Högskolan i Bodö.
    Embodied suffering: experiences of fear in adolescent girls with cancer2008In: Journal of Child Health Care, ISSN 1367-4935, E-ISSN 1741-2889, Vol. 12, no 2, p. 129-143Article in journal (Refereed)
    Abstract [en]

    Previously, fear in adolescents with cancer has been sparsely described from an emic perspective. The aim of this study was to illuminate fear in adolescents with personal experience of cancer. The participants were six adolescent girls between the age of 14 and 16 years who were no longer under active treatment for cancer but still went for regular check-ups. Open interviews were conducted. Data were analysed according to the phenomenological hermeneutic method. In the result one main theme was identified: `an embodied fear — a threat to the personal self'. This theme was built up by three separate but intertwined themes: `experiencing fear related to the physical body', `experiencing existential fear' and `experiencing fear related to the social self'. In the comprehensive understanding the fear was interpreted from youth cultural aspects as well as a holistic perspective. The importance of professionals taking the whole person and their situation into account when meeting the fear is underlined.

  • 19.
    Andrén, Ove
    et al.
    Örebro University, School of Health and Medical Sciences.
    Fall, Katja
    Andersson, Swen-Olof
    Rubin, Mark A.
    Bismar, Tarek A.
    Karlsson, M.
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Mucci, Lorelei A.
    MUC-1 gene is associated with prostate cancer death: a 20-year follow-up of a population-based study in Sweden2007In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 97, no 6, p. 730-734Article in journal (Refereed)
    Abstract [en]

    Anti-adhesion mucins have proven to play an important part in the biology of several types of cancer. Therefore, we test the hypothesis that altered expression of MUC-1 is associated with prostate cancer progression. We retrieved archival tumour tissue from a population-based cohort of 195 men with localised prostate cancer (T1a-b, Nx, M0) that has been followed for up to 20 years with watchful waiting. Semi-automated, quantitative immunohistochemistry was undertaken to evaluate MUC-1 expression. We modelled prostate cancer-specific death as a function of MUC-1 levels accounting for age, Gleason grade and tumour extent, and calculated age-adjusted and multivariate adjusted hazard ratios (HR). Men that had tumours with an MUC-intensity lower or higher than normal tissue had a higher risk of dying in prostate cancer, independent of tumour extent and Gleason score (HR 5.1 and 4.5, respectively). Adjustment for Gleason grade and tumour stage did not alter the results. Men with a Gleason score >=7 and MUC-1 deviating from the normal had a 17 (RR=17.1 95% confidence interval=2.3–128) times higher risk to die in prostate cancer compared with men with Gleason score <7 and normal MUC-1 intensity. In summary, our data show that MUC-1 is an independent prognostic marker for prostate cancer death.

  • 20. Andrén, Ove
    et al.
    Garmo, H.
    Mucci, L.
    Andersson, Swen-Olof
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Fall, Katja
    Incidence and mortality of incidental prostate cancer: a Swedish register-based study2009In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 100, no 1, p. 170-173Article in journal (Refereed)
    Abstract [en]

    In a national register-based study of incidence trends and mortality of incidental prostate cancer in Sweden, we found that a significant proportion (26.6%) of affected men diagnosed died of their disease, which challenges earlier descriptions of incidental prostate cancer as a non-lethal disease.

  • 21.
    Andrén, Ove
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Widmark, A.
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Fält, A.
    Ulvskog, E.
    Örebro University, School of Medical Sciences. Department of Oncology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Karlsson, C. Thellenberg
    Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
    Hjälm-Eriksson, M.
    Department of Oncology, Karolinska Institute, Stockholm, Sweden.
    Cabazitaxel followed by androgen deprivation therapy (ADT) significantly improves time to progression in patients with newly diagnosed metastatic hormone sensitive prostate cancer (mHSPC): A randomized, open label, phase III, multicenter trial2017In: Annals of Oncology, ISSN 0923-7534, E-ISSN 1569-8041, Vol. 28, no Suppl. 5, article id 811PArticle in journal (Other academic)
  • 22.
    Arora, Manish
    et al.
    Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, USA; Cellular and Molecular Pathology Research Unit, Department of Oral Pathology and Oral Medicine, University of Sydney, Sydney, Australia; Population Oral Health, University of Sydney, Sydney, Australia.
    Weuve, Jennifer
    Environmental and Occupational Medicine and Epidemiology Program, Harvard School of Public Health, Boston, USA; Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Fall, Katja
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology, Harvard School of Public Health, Boston, USA.
    Pedersen, Nancy L.
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Mucci, Lorelei A.
    Department of Epidemiology, Harvard School of Public Health, Boston, USA; Channing Laboratory, Brigham and Women's Hospital, Harvard Medical School, Boston, USA.
    An exploration of shared genetic risk factors between periodontal disease and cancers: a prospective co-twin study2010In: American Journal of Epidemiology, ISSN 0002-9262, E-ISSN 1476-6256, Vol. 171, no 2, p. 253-9Article in journal (Refereed)
    Abstract [en]

    Biologic mechanisms underlying associations of periodontal disease with cancers remain unknown. The authors propose that both conditions share common genetic risk factors. They analyzed associations between baseline periodontal disease, measured by questionnaire-recorded tooth mobility, and incident cancers, identified by linkage with national registries, between 1963 and 2004 in 15,333 Swedish twins. The authors used co-twin analyses to control for familial factors and undertook analyses restricted to monozygotic twins to further control for confounding by genetic factors. They observed 4,361 cancer cases over 548,913 person-years. After adjustment for covariates, baseline periodontal disease was associated with increased risk of several cancers ranging from 15% for total cancer (proportional hazard ratio (HR) = 1.15, 95% confidence interval (CI): 1.01, 1.32) to 120% for corpus uterine cancer (HR = 2.20, 95% CI: 1.16, 4.18). Periodontal disease was also associated with increased risk of colorectal (HR = 1.62, 95% CI: 1.13, 2.33), pancreatic (HR = 2.06, 95% CI: 1.14, 3.75), and prostate (HR = 1.47, 95% CI: 1.04, 2.07) cancers. In co-twin analyses, dizygotic twins with baseline periodontal disease showed a 50% increase in total cancer risk (HR = 1.50, 95% CI: 1.04, 2.17), but in monozygotic twins this association was markedly attenuated (HR = 1.07, 95% CI: 0.63, 1.81). Similar patterns emerged for digestive tract cancers, suggesting that shared genetic risk factors may partially explain associations between periodontal disease and cancers.

  • 23.
    Baban, Bayar
    et al.
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Ljungqvist, Olle
    Örebro University, School of Medical Sciences. Department of Surgery, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Särndahl, Eva
    Örebro University, School of Medical Sciences. iRiSC – Inflammatory Response and Infection Susceptibility Centre, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Inflammasome activation, colonic cancer and glucose metabolism2016In: Clinical Nutrition ESPEN, ISSN 2405-4577, Vol. 12, article id e37Article in journal (Refereed)
    Abstract [en]

    Objectives: To study the association between inflammasome activation (a potent initiator of inflammation acting via caspase-1 and maturation of interleukin-1β), colonic cancer and glucose metabolism.

    Methods: Five patients with colon cancer and ten matched controls without cancer were measured for insulin sensitivity using the hyperinsulinemic euglycemic clamp. For detection of inflammasome activation the caspase-1 activity, determined by detecting FLICA using flow cytometry, was measured in both monocytes and granulocytes at the start of, and at 120 minutes into the clamp. Descriptive and analytical statistics were performed using nonparametric methods by SPSS.

    Results: There was no difference in levels of insulin sensitivity between the two groups (p=0.09). The cancer patients had significantly lower levels of caspase-1 both in monocytes (p<0.05) and granulocytes (p<0.05) compared with the controls. However both patients and controls had significantly higher levels of both mono- and granulocyte caspase-1 activity at 120 minutes into the clamp as compared to at start (p<0.05). Patients showed an overall higher relative increase in caspase-1 during the clamp, however this finding did not reach statistical significance (monocytes; p=0.27, granulocytes; p=0.22).

  • 24. Bahmanyar, S.
    et al.
    Montgomery, Scott M.
    Örebro University, School of Health and Medical Sciences.
    Hillert, J.
    Ekbom, A.
    Olsson, T.
    Cancer risk among patients with multiple sclerosis and their parents2009In: Neurology, ISSN 0028-3878, E-ISSN 1526-632X, Vol. 72, no 13, p. 1170-1177Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: We investigated cancer risk among patients with multiple sclerosis (MS) and whether variation by age at MS diagnosis helps to elucidate mechanisms underlying the previously reported reduced cancer risk. We also studied cancer risk among parents to ascertain if MS susceptibility genes may confer protection against cancer in relatives. METHODS: Cox proportional hazards regression, adjusted for age, sex, area, and socioeconomic index, estimated cancer risk among 20,276 patients with MS and 203,951 individuals without MS, using Swedish general population register data. Similar analyses were conducted among 11,284 fathers and 12,006 mothers of patients with MS, compared with 123,158 fathers and 129,409 mothers of controls. RESULTS: With an average of 35 years of follow-up, there was a decreased overall cancer risk among patients with MS (hazard ratio = 0.91, 0.87-0.95). Increased risks were observed for brain tumors (1.44, 1.21-1.72) and urinary organ cancer (1.27, 1.05-1.53). Parents of patients with MS did not have a notably increased or decreased overall cancer risk. CONCLUSIONS: The reduction in cancer risk in patients with multiple sclerosis (MS) may result from behavioral change, treatment, or we speculate that some immunologic characteristics of MS disease activity improve antitumor surveillance. The lack of association among parents indicates that a simple inherited characteristic is unlikely to explain the reduced cancer risk among patients with MS. MS is associated with increased risk for some cancers, such as of urinary organs and brain tumors (although surveillance bias may be responsible).

  • 25.
    Behrens, Thomas
    et al.
    Bremen Institute of Prevention Research & Social Medicine, Bremen, Germany; Institute of Prevention & Occupational Medicine of German Social Accidents Insurance, Bochum, Germany.
    Lynge, Elsebeth
    Inst Publ Hlth, Univ Copenhagen, Copenhagen, Denmark..
    Cree, Ian
    Inst Ophthalmol, University College London (UCL), London, England.
    Lutz, Jean-Michel
    National Institute for Cancer Epidemiology and Registration (NICER), Univ Zurich, Zurich, Switzerland.
    Eriksson, Mikael
    Dept of Oncology, Lund University Hospital, Lund, Sweden..
    Guenel, Pascal
    Centre de recherche en épidémiologie et santé des populations (CESP), French National Institute of Health and Medical Research (INSERM), Villejuif, France; Univ Paris Sud, Villejuif, France.
    Merletti, Franco
    Cancer Epidemiology Unit, Univ Turin, Piemonte, Italy; ll Centro di Riferimento per l'Epidemiologia e la Prevenzione Oncologica (CPO), Piemonte, Italy.
    Morales-Suarez-Varela, Maria
    Dept of Prevention Medicine, Unit Public Health & Environmental Care, University Valencia, Valencia, Spain; CIBER Act Epidemiology & Public Health, Res Grp CIBER CB06, Valencia, Spain; Center Public Health Research CSISP, Valencia, Spain.
    Afonso, Noemia
    Med Oncol Serv, Inst Portugues Oncol Francisco Gentil, Oporto, Portugal.
    Stengrevics, Aivars
    Latvia Canc Registry, Riga, Latvia.
    Fevotte, Joelle
    Umrestte UCB Lyon 1 InVS Inrets, Lyon, France.
    Sabroe, Svend
    Dept Epidemiol, Univ Aarhus, Aarhus, Denmark..
    Llopis-Gonzalez, Agustin
    Dept Prevent Med, Unit Publ Hlth & Environm Care, Univ Valencia, Valencia, Spain; CIBER Act Epidemiol & Publ Hlth, Res Grp CIBER CB06, Valencia, Spain.
    Gorini, Giuseppe
    Environm & Occupat Epidemiol Unit, ISPO Canc Prevent & Res Inst, Florence, Italy.
    Hardell, Lennart
    Department of Oncology, Örebro University Hospital, Region Örebro län, Örebro, Sweden.
    Stang, Andreas
    Inst Clin Epidemiol, Univ Halle Wittenberg, Halle, Germany; Inst Med Informat Biometry & Epidemiol, Univ Duisburg Essen, Essen, Germany..
    Ahrens, Wolfgang
    Bremen Inst Prevent Res & Social Med, Bremen, Germany; Inst Med Informat Biometry & Epidemiol, Univ Duisburg Essen, Essen, Germany.
    Pesticide exposure in farming and forestry and the risk of uveal melanoma2012In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 23, no 1, p. 141-151Article in journal (Refereed)
    Abstract [en]

    Since pesticides are disputed risk factors for uveal melanoma, we studied the association between occupational pesticide exposure and uveal melanoma risk in a case-control study from nine European countries.

    Incident cases of uveal melanoma and population as well as hospital controls were included and frequency-matched by country, 5-year age groups and sex. Self-reported exposure was quantified with respect to duration of exposure and pesticide application method. We calculated the exposure intensity level based on application method and use of personal protective equipment. Odds ratios (OR) and 95% confidence intervals (95% CI) were estimated by unconditional logistic regression analyses and adjusted for several potential confounders.

    293 case and 3,198 control subjects were interviewed. We did not identify positive associations with activities in farming or forestry, pesticide application or pesticide mixing. No consistent positive associations were seen with exposure intensity level scores either. The only statistically significantly raised association in this study was for exposure to chemical fertilizers in forestry (OR = 8.93; 95% CI 1.73-42.13), but this observation was based on only six exposed subjects. Results did not change when we restricted analyses to morphologically verified cases and excluded proxy interviews as well as cancer controls. We did not observe effect modification by sex or eye color.

    Risk estimates for pesticide exposures and occupational activities in agriculture and forestry were not increased and did not indicate a hormonal mechanism due to these exposures.

  • 26.
    Bergengren, Lovisa
    et al.
    Örebro University, School of Health Sciences. Department of Women’s Health, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Kaliff, Malin
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Lillsunde-Larsson, Gabriella
    Örebro University, School of Health Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Karlsson, Mats
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Helenius, Gisela
    Örebro University, School of Medical Sciences. Department of Laboratory Medicine, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Comparison between professional sampling and self-sampling for HPV-based cervical cancer screening among postmenopausal women2018In: International Journal of Gynecology & Obstetrics, ISSN 0020-7292, E-ISSN 1879-3479, Vol. 142, no 3, p. 359-364Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE: To investigate whether self-sampling is as reliable as professional sampling for HPV testing and genotype detection among postmenopausal women.

    METHODS: In the present prospective cross-sectional study, women in Örebro County, Sweden, who had high-risk HPV (hrHPV) and normal cytology results in exit screening tests conducted in between January 1, 2012, and December 31, 2014, were invited to follow-up screenings between February 24, 2015 and May 15, 2015, that included professional sampling and self-sampling. HPV genotypes were identified by a DNA-based assay that could detect 35 HPV genotypes. Findings between the different sampling methods were compared.

    RESULTS: Of 143 women who participated, 119 returned a self-sample. Completely concordant results were observed in 67 of these samples when both hrHPV and low-risk HPV genotypes were analyzed. Overall, 99 (83.2%) women had the same clinically relevant finding from both sampling methods. Twenty women had discordant hrHPV results (hrHPV detected in 10 self-samples vs 10 professionally collected samples; Cohen κ 0.66, 95% confidence interval 0.53-0.80). There was no significant difference between the two sampling methods for clinically significant infections (P>0.99) or extended genotyping (P=0.827).

    CONCLUSION: Postmenopausal women could be offered self-sampling devices to increase screening-program coverage while maintaining test quality.

  • 27.
    Bergfelt, Emma
    et al.
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Kozlowski, Piotr
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Ahlberg, Lucia
    Department of Haematology, University Hospital of Linköping, Linköping, Sweden.
    Hulegårdh, Erik
    Department of Haematology and Coagulation, Sahlgrenska University Hospital, Göteborg, Sweden.
    Hägglund, Hans
    Division of Haematology, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Karlsson, Karin
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Markuszewska-Kuczymska, Alicja
    Department of Haematology, Cancer Center, University Hospital of Umeå, Umeå , Sweden.
    Tomaszewska-Toporska, Beata
    Department of Haematology, Skåne University Hospital, Lund, Sweden.
    Smedmyr, Bengt
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Åström, Maria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Amini, Rose-Marie
    Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Hallböök, Helene
    Department of Medical Sciences, Haematology, Uppsala University, Uppsala, Sweden.
    Satisfactory outcome after intensive chemotherapy with pragmatic use of minimal residual disease (MRD) monitoring in older patients with Philadelphia-negative B cell precursor acute lymphoblastic leukaemia: a Swedish registry-based study2015In: Medical Oncology, ISSN 1357-0560, E-ISSN 1559-131X, Vol. 32, no 4, article id 135Article in journal (Refereed)
    Abstract [en]

    The introduction of minimal residual disease (MRD) monitoring, in the Swedish national guidelines for acute lymphoblastic leukaemia, was evaluated in 35 patients aged 46-79 years (median 61), who were diagnosed from 2007 to 2011 and treated with high-intensity, block-based chemotherapy (ABCDV/VABA induction). Both a high complete remission rate (91 %) and acceptable overall survival (OS) rate (47 %) at 5 years were achieved. MRD by flow cytometry was measured in 73 % of the patients reaching complete remission after the first course, but was omitted by the clinicians for eight patients who were either over 70 years of age or already met conventional high-risk criteria. Factors negatively influencing OS were age over 65 years and WHO status >= 2. MRD < 0.1 % after induction had positive impact on continuous complete remission but not on OS. Only five patients were allocated to allogeneic haematopoietic stem cell transplantation in first remission, mainly due to conventional high risk factors. Thus, use of intensive remission induction therapy is effective in a selection of older patients. In a population for whom the possibilities of treatment escalation are limited, the optimal role of MRD monitoring remains to be determined.

  • 28. Bergkvist, Leif
    et al.
    de Boniface, Jana
    Jönsson, Per-Ebbe
    Ingvar, Christian
    Liljegren, Göran
    Örebro University, School of Health and Medical Sciences.
    Frisell, Jan
    Axillary recurrence rate after negative sentinel node biopsy in breast cancer: three-year follow-up of the Swedish Multicenter Cohort Study2008In: Annals of Surgery, ISSN 0003-4932, E-ISSN 1528-1140, Vol. 247, no 1, p. 150-156Article in journal (Refereed)
    Abstract [en]

    Background: Sentinel lymph node biopsy is an established staging method in early breast cancer. After a negative biopsy, most institutions will not perform a completion axillary dissection. The present study reports the current axillary recurrence (AR) rate, overall and disease-free survival in the Swedish Multicenter Cohort Study.

    Methods: From 3534 patients with primary breast cancer ≤3 cm prospectively enrolled in the Swedish multicenter cohort study, 2246 with a negative sentinel node biopsy and no further axillary surgery were selected. Follow-up consisted of annual clinical examination and mammography. Twenty-six hospitals and 131 surgeons contributed to patient accrual.

    Results: After a median follow-up time of 37 months (0-75), the axilla was the sole initial site of recurrence in 13 patients (13 of 2246, 0.6%). In another 7 patients, axillary relapse occurred after or concurrently with a local recurrence in the breast, and in a further 7 cases, it coincided with distant or extra-axillary lymphatic metastases. Thus, a total of 27 ARs were identified (27 of 2246, 1.2%). The overall 5-year survival was 91.6% and disease-free survival 92.1%.

    Conclusions: This is the first report from a national multicenter study that covers, not only highly specialized institutions but also small community hospitals with just a few procedures per year. Despite this heterogeneous background, the results lie well within the range of AR rates published internationally (0%-3.6%). The sentinel node biopsy procedure seems to be safe in a multicenter setting. Nevertheless, long-term follow-up data should be awaited before firm conclusions are drawn.

  • 29.
    Bergström, A.
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Hsieh, C. C.
    Cancer Center, UMass Medical School, Worcester, MA, USA; Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden; Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Lu, C. M.
    Cancer Center, UMass Medical School, Worcester, MA, USA; Department of Urology, Tian-Sheng Memorial Hospital, Pingtung, Taiwan.
    Cook, N. R.
    Division of Preventive Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA.
    Wolk, A.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Obesity and renal cell cancer: a quantitative review2001In: British Journal of Cancer, ISSN 0007-0920, E-ISSN 1532-1827, Vol. 85, no 7, p. 984-990Article in journal (Refereed)
    Abstract [en]

    Obesity has been associated with an increased risk of renal cell cancer among women, while the evidence for men is considered weaker. We conducted a quantitative summary analysis to evaluate the existing evidence that obesity increases the risk of renal cell cancer both among men and women. We identified all studies examining body weight in relation to kidney cancer, available in MEDLINE from 1966 to 1998. The quantitative summary analysis was limited to studies assessing obesity as body mass index (BMI, kg m(-2)), or equivalent. The risk estimates and the confidence intervals were extracted from the individual studies, and a mixed effect weighted regression model was used. We identified 22 unique studies on each sex, and the quantitative analysis included 14 studies on men and women, respectively. The summary relative risk estimate was 1.07 (95% CI 1.05-1.09) per unit of increase in BMI (corresponding to 3 kg body weight increase for a subject of average height). We found no evidence of effect modification by sex. Our quantitative summary shows that increased BMI is equally strongly associated with an increased risk of renal cell cancer among men and women.

  • 30.
    Bergström, A.
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    Medical Epidemiology, Karolinska Institutet, Stockholm; Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Wolk, A.
    Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Birth weight and risk of renal cell cancer2001In: Kidney International, ISSN 0085-2538, E-ISSN 1523-1755, Vol. 59, no 3, p. 1110-1113Article in journal (Refereed)
    Abstract [en]

    Background: The prenatal period has been suggested to be important for future cancer risk. Conditions in utero are also important for the development of the kidney, and birth weight, a marker of fetal nutrition and growth, is linearly correlated with the number of nephrons and the structural and functional unit of the kidney. An association between birth weight and renal cell cancer, the major form of kidney cancer, is biologically plausible, but has never been studied.

    Methods: We conducted a population-based, case-controlled study in Sweden of men and women aged 20 to 79 years. We collected self-reported information on categories of birth weight from 648 patients with newly diagnosed renal cell cancer and from 900 frequency-matched control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as estimates of the relative risks.

    Results: An increased risk of renal cell cancer was observed among men with a birth weight of > or =3500 g (adjusted OR = 1.3, 95% CI, 1.0 to 1.8) compared with men with a birth weight between 3000 and 3499 g, especially in the subgroup without hypertension or diabetes (adjusted OR = 1.8, 95% CI, 1.2 to 2.6). No clear association among men with a birth weight <3000 g or among women was found.

    Conclusions: Our study shows that conditions in utero, reflected by birth weight, might affect the risk of renal cell cancer in adulthood. It is unclear why no association was found among women. Further studies, based on weight from birth certificates, are needed to clarify this relationship.

  • 31.
    Bergström, A.
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Moradi, T.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden; Department of Urology, Sundsvall Hospital, Sundsvall, Sweden.
    Nyren, O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Adami, H. O.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Harvard Center for Cancer Prevention, Harvard School of Public Health, Boston, MA, USA.
    Wolk, A.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Occupational physical activity and renal cell cancer: a nationwide cohort study in Sweden1999In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 83, no 2, p. 186-91Article in journal (Refereed)
    Abstract [en]

    The causes of renal cell cancer remain incompletely understood. In one previous retrospective case-control study, high occupational physical activity has been associated with a decreased risk among men, but not among women. Our aim was to investigate the association between occupational physical activity and renal cell cancer in a large cohort in Sweden. A cohort of Swedish men and women was identified in the nationwide censuses in 1960 and 1970, and the reported occupations were classified into 4 levels of physical demands. Follow-up from 1971 through 1989 was accomplished through record linkages to the Swedish Cancer Registry. Multivariate Poisson regression models were used to estimate relative risk (RR) and 95% confidence intervals (CI). We found a monotonic increase in risk of renal cell cancer with decreasing level of occupational physical activity among men (p for trend <0.001). After adjustment for socio-economic status, place of residence, and calendar year of follow-up, men with long-term sedentary jobs had a 25% (RR = 1.25, 95% CI 1.02-1.53) increased risk compared to men with physically demanding occupations. Among women there was no association, the dose-risk trend was not significant (p for trend >0.50). Occupational physical activity was inversely associated with renal cell cancer among men. The absence of association among women might be due to smaller range of exposure, confounding by household work or reproductive factors, or to a difference in biological response to physical activity in men and women.

  • 32.
    Bergström, A.
    et al.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Terry, P.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Lindblad, Per
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Lichtenstein, P.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Ahlbom, A.
    The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Feychting, M.
    The Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden.
    Wolk, A.
    Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Physical activity and risk of renal cell cancer2001In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 92, no 1, p. 155-157Article in journal (Refereed)
    Abstract [en]

    The relation between physical activity and renal cell cancer is unclear. High occupational physical activity has been associated with a decreased risk of renal cell cancer among men-but not among women-in two previous studies, while no association has been found for leisure time physical activity. Our aim was to investigate the association between occupational and leisure time physical activity in a prospective cohort of 17,241 Swedish twins. Information on physical activity and a wide range of potential confounding factors was obtained through a mailed questionnaire. During follow-up from 1967 through 1997 we identified 102 cases of renal cell cancer. We found no evidence of an inverse association between either occupational or leisure time physical activity and risk of renal cell cancer in this prospective cohort.

  • 33. Bill-Axelson, Anna
    et al.
    Holmberg, Lars
    Filén, Frej
    Ruutu, Mirja
    Garmo, Hans
    Busch, Christer
    Nordling, Stig
    Häggman, Michael
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences.
    Bratell, Stefan
    Spångberg, Anders
    Palmgren, Juni
    Adami, Hans-Olov
    Johansson, Jan-Erik
    Örebro University, School of Health and Medical Sciences.
    Radical prostatectomy versus watchful waiting in localized prostate cancer: the Scandinavian prostate cancer group-4 randomized trial2008In: Journal of the National Cancer Institute, ISSN 0027-8874, E-ISSN 1460-2105, Vol. 100, no 16, p. 1144-1154Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: The benefit of radical prostatectomy in patients with early prostate cancer has been assessed in only one randomized trial. In 2005, we reported that radical prostatectomy improved prostate cancer survival compared with watchful waiting after a median of 8.2 years of follow-up. We now report results after 3 more years of follow-up.

    METHODS: From October 1, 1989, through February 28, 1999, 695 men with clinically localized prostate cancer were randomly assigned to radical prostatectomy (n = 347) or watchful waiting (n = 348). Follow-up was complete through December 31, 2006, with histopathologic review and blinded evaluation of causes of death. Relative risks (RRs) were estimated using the Cox proportional hazards model. Statistical tests were two-sided.

    RESULTS: During a median of 10.8 years of follow-up (range = 3 weeks to 17.2 years), 137 men in the surgery group and 156 in the watchful waiting group died (P = .09). For 47 of the 347 men (13.5%) who were randomly assigned to surgery and 68 of the 348 men (19.5%) who were not, death was due to prostate cancer. The difference in cumulative incidence of death due to prostate cancer remained stable after about 10 years of follow-up. At 12 years, 12.5% of the surgery group and 17.9% of the watchful waiting group had died of prostate cancer (difference = 5.4%, 95% confidence interval [CI] = 0.2 to 11.1%), for a relative risk of 0.65 (95% CI = 0.45 to 0.94; P = .03). The difference in cumulative incidence of distant metastases did not increase beyond 10 years of follow-up. At 12 years, 19.3% of men in the surgery group and 26% of men in the watchful waiting group had been diagnosed with distant metastases (difference = 6.7%, 95% CI = 0.2 to 13.2%), for a relative risk of 0.65 (95% CI = 0.47 to 0.88; P = .006). Among men who underwent radical prostatectomy, those with extracapsular tumor growth had 14 times the risk of prostate cancer death as those without it (RR = 14.2, 95% CI = 3.3 to 61.8; P < .001).

    CONCLUSION: Radical prostatectomy reduces prostate cancer mortality and risk of metastases with little or no further increase in benefit 10 or more years after surgery. 

  • 34.
    Bill-Axelson, Anna
    et al.
    Dept. Urology, Uppsala University Hospital, Uppsala, Sweden; Dept, Pathology & Oncology, Div. Clinical Cancer Epidemiology, Karolinska Institute, Stockholm, Sweden.
    Holmberg, Lars
    Regional Oncology Center, Uppsala University Hospital, Uppsala, Sweden; School of Medicine, Division of Cancer Studies, Kings College London, London, England.
    Ruutu, Mirja
    Cent Hosp, Dept Urol, Univ Helsinki, Helsinki, Finland.
    Garmo, Hans
    Reg Oncol Ctr, Univ Uppsala Hospital, Uppsala, Sweden; Sch Med, Div Canc Studies, Kings College London, London, UK.
    Stark, Jennifer R
    Deptartment of Urology, Örebro University Hospital, Örebro, Sweden; Dept Med, Channing Lab, Brigham & Womens Hospital, Boston MA, USA; Sch Med, Harvard University, Boston MA, USA.
    Busch, Christer
    Dept Pathol, Uppsala University Hospital, Uppsala, Sweden.
    Nordling, Stig
    Cent Hosp, Dept Pathol, Univ Helsinki, Helsinki, Finland.
    Häggman, Michael
    Dept Urology, Uppsala University Hospital, Uppsala, Sweden.
    Andersson, Swen-Olof
    Örebro University, School of Health and Medical Sciences. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Bratell, Stefan
    Dept Urology, Borås Hospital, Borås, Sweden.
    Spångberg, Anders
    Dept Urology, Linköping University Hospital, Linköping, Sweden.
    Palmgren, Juni
    Dept Med Epidemiol & Biostat, Karolinska Institute, Stockholm, Sweden.
    Steineck, Gunnar
    Dept, Pathology & Oncology, Div. Clinical Cancer Epidemiology, Karolinska Institute, Stockholm, Sweden; Div Clin Canc Epidemiol, Sahlgrenska Academy, Gothenburg, Sweden.
    Adami, Hans-Olov
    Dept Med Epidemiol & Biostat, Karolinska Institute, Stockholm, Sweden; School of Publ Health, Dept Epidemiology, Harvard Univ, Boston MA, USA.
    Johansson, J-E
    Örebro University, School of Health and Medical Sciences. Dept Urol, Örebro University Hospital, Örebro, Sweden; Center of Assessment Med Technology, Örebro University Hospital, Örebro, Sweden.
    Radical prostatectomy versus watchful waiting in early prostate cancer2011In: New England Journal of Medicine, ISSN 0028-4793, E-ISSN 1533-4406, Vol. 364, no 18, p. 1708-1717Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: In 2008, we reported that radical prostatectomy, as compared with watchful waiting, reduces the rate of death from prostate cancer. After an additional 3 years of follow-up, we now report estimated 15-year results.

    METHODS: From October 1989 through February 1999, we randomly assigned 695 men with early prostate cancer to watchful waiting or radical prostatectomy. Follow-up was complete through December 2009, with histopathological review of biopsy and radical-prostatectomy specimens and blinded evaluation of causes of death. Relative risks, with 95% confidence intervals, were estimated with the use of a Cox proportional-hazards model.

    RESULTS: During a median of 12.8 years, 166 of the 347 men in the radical-prostatectomy group and 201 of the 348 in the watchful-waiting group died (P=0.007). In the case of 55 men assigned to surgery and 81 men assigned to watchful waiting, death was due to prostate cancer. This yielded a cumulative incidence of death from prostate cancer at 15 years of 14.6% and 20.7%, respectively (a difference of 6.1 percentage points; 95% confidence interval [CI], 0.2 to 12.0), and a relative risk with surgery of 0.62 (95% CI, 0.44 to 0.87; P=0.01). The survival benefit was similar before and after 9 years of follow-up, was observed also among men with low-risk prostate cancer, and was confined to men younger than 65 years of age. The number needed to treat to avert one death was 15 overall and 7 for men younger than 65 years of age. Among men who underwent radical prostatectomy, those with extracapsular tumor growth had a risk of death from prostate cancer that was 7 times that of men without extracapsular tumor growth (relative risk, 6.9; 95% CI, 2.6 to 18.4).

    CONCLUSIONS: Radical prostatectomy was associated with a reduction in the rate of death from prostate cancer. Men with extracapsular tumor growth may benefit from adjuvant local or systemic treatment.

  • 35.
    Blattner, Mirjam
    et al.
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York, USA.
    Lee, Daniel J.
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York, USA; Dept Urol, Weill Med Coll, Cornell Univ, New York, USA.
    O'Reilly, Catherine
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA.
    Park, Kyung
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA.
    MacDonald, Theresa Y.
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA.
    Khani, Francesca
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA.
    Turner, Kevin R.
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA.
    Chiu, Ya-Lin
    Dept Biostat & Epidemiol, Weill Med Coll, Cornell Univ, New York NY, USA.
    Wild, Peter J.
    Inst Surg Pathol, Univ Zurich Hosp, Zurich, Switzerland.
    Dolgalev, Igor
    Human Oncol & Pathogenesis Program, Mem Sloan Kettering Canc Ctr, New York NY, USA.
    Heguy, Adriana
    Human Oncol & Pathogenesis Program, Mem Sloan Kettering Canc Ctr, New York NY, USA.
    Sboner, Andrea
    Dept Pathol & Lab Med, Inst Precis Med, New York NY, USA; Weill Med Coll, Cornell Univ, Inst Computat Biomed, New York, NY, USA; Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA.
    Ramazangolu, Sinan
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA; Inst Computat Biomed, Weill Med Coll, Cornell Univ, New York NY, USA.
    Hieronymus, Haley
    Inst Computat Biomed, Weill Med Coll, Cornell Univ, New York NY, USA.
    Sawyers, Charles
    Mem Sloan Kettering Canc Ctr, Human Oncol & Pathogenesis Program, New York NY, USA.
    Tewari, Ashutosh K.
    Dept Urol, Weill Med Coll, Cornell Univ, New York NY, USA.
    Moch, Holger
    Inst Surg Pathol, Univ Zurich Hosp, Zurich, Switzerland.
    Yoon, Ghil Suk
    Sch Med, Dept Pathol, Kyungpook Natl Univ, Taegu, South Korea.
    Known, Yong Chul
    Sch Med, Dept Pathol, Catholic Univ Daegu, Taegu, South Korea.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Dept Urol, Örebro University Hospital, Örebro, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Demichelis, Francecsa
    Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA; Ctr Integrat Biol, Univ Trento, Trento, Italy.
    Mosquera, Juan Miguel
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA.
    Robinson, Brian D.
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA; Dept Urol, Weill Med Coll, Cornell Univ, New York NY, USA .
    Barbieri, Christopher E.
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA; Dept Urol, Weill Med Coll, Cornell Univ, New York NY, USA .
    Rubin, Mark A.
    Dept Pathol & Lab Med, Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA; Dept Urol, Weill Med Coll, Cornell Univ, New York NY, USA; Inst Precis Med, Weill Med Coll, Cornell Univ, New York NY, USA .
    SPOP Mutations in Prostate Cancer across Demographically Diverse Patient Cohorts2014In: Neoplasia, ISSN 1522-8002, E-ISSN 1476-5586, Vol. 16, no 1, p. 14-U34Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Recurrent mutations in the Speckle-Type POZ Protein (SPOP) gene occur in up to 15% of prostate cancers. However, the frequency and features of cancers with these mutations across different populations is unknown.

    OBJECTIVE: To investigate SPOP mutations across diverse cohorts and validate a series of assays employing high-resolution melting (HRM) analysis and Sanger sequencing for mutational analysis of formalin-fixed paraffin-embedded material.

    DESIGN, SETTING, AND PARTICIPANTS: 720 prostate cancer samples from six international cohorts spanning Caucasian, African American, and Asian patients, including both prostate-specific antigen-screened and unscreened populations, were screened for their SPOP mutation status. Status of SPOP was correlated to molecular features (ERG rearrangement, PTEN deletion, and CHD1 deletion) as well as clinical and pathologic features.

    RESULTS AND LIMITATIONS: Overall frequency of SPOP mutations was 8.1% (4.6% to 14.4%), SPOP mutation was inversely associated with ERG rearrangement (P < .01), and SPOP mutant (SPOPmut) cancers had higher rates of CHD1 deletions (P < .01). There were no significant differences in biochemical recurrence in SPOPmut cancers. Limitations of this study include missing mutational data due to sample quality and lack of power to identify a difference in clinical outcomes.

    CONCLUSION: SPOP is mutated in 4.6% to 14.4% of patients with prostate cancer across different ethnic and demographic backgrounds. There was no significant association between SPOP mutations with ethnicity, clinical, or pathologic parameters. Mutual exclusivity of SPOP mutation with ERG rearrangement as well as a high association with CHD1 deletion reinforces SPOP mutation as defining a distinct molecular subclass of prostate cancer.

  • 36.
    Blattner, Mirjam
    et al.
    Weill Cornell Med Coll, New York NY, USA.
    Lee, Daniel
    Weill Cornell Med Coll, New York NY, USA.
    O'Reilly, Catherine
    Weill Cornell Med Coll, New York NY, USA.
    Park, Kyung
    Weill Cornell Med Coll, New York NY, USA.
    MacDonald, Theresa Y.
    Weill Cornell Med Coll, New York NY, USA.
    Khani, Francesca
    Weill Cornell Med Coll, New York NY, USA.
    Turner, Kevin
    Weill Cornell Med Coll, New York NY, USA.
    Wild, Peter J.
    Univ Zurich Hosp, Zurich, Switzerland.
    Hieronymus, Haley
    Mem Sloan Kettering Canc Ctr, New York NY, USA.
    Sawyers, Charles L.
    Mem Sloan Kettering Canc Ctr, New York NY, USA.
    Tewari, Ashutosh K.
    Weill Cornell Med Coll, New York, USA.
    Moch, Holger
    Univ Zurich Hosp, Zurich, Switzerland.
    Yoon, Ghil Suk
    Sch Med, Kyungpook Natl Univ, Daegu, South Korea.
    Andrén, Ove
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Fall, Katja
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Mosquera, Juan Miguel
    Weill Cornell Med Coll, New York NY, USA.
    Robinson, Brian D.
    Weill Cornell Med Coll, New York NY, USA.
    Sboner, Andrea
    Weill Cornell Med Coll, New York NY, USA.
    Barbierie, Christopher E.
    Weill Cornell Med Coll, New York NY, USA.
    Rubin, Mark A.
    Weill Cornell Med Coll, New York NY, USA.
    SPOP mutations in prostate cancer across demographically diverse patient cohorts2014In: Cancer Research, ISSN 0008-5472, E-ISSN 1538-7445, Vol. 74, no 19, article id 2244Article in journal (Other academic)
  • 37.
    Blomberg, Karin
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Wengström, Yvonne
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department NVS, Section for Nursing, Karolinska Institutet, Stockholm, Sweden.
    Sundberg, Kay
    Department NVS, Section for Nursing, Karolinska Institutet, Stockholm, Sweden.
    Browall, Maria
    Department NVS, Section for Nursing, Karolinska Institutet, Stockholm, Sweden; School of Life Sciences, University of Skövde, Skövde, Sweden.
    Isaksson, Ann-Kristin
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Hälleberg Nyman, Maria
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Langius-Eklöf, Ann
    Department NVS, Section for Nursing, Karolinska Institutet, Stockholm, Sweden.
    Symptoms and self-care strategies during and six months after radiotherapy for prostate cancer: Scoping the perspectives of patients, professionals and literature2016In: European Journal of Oncology Nursing, ISSN 1462-3889, E-ISSN 1532-2122, Vol. 21, p. 139-145Article in journal (Refereed)
    Abstract [en]

    Purpose: Under-diagnosed and uncontrolled symptoms in patients with prostate cancer during radiotherapy can have a negative impact on the individual's quality of life. An opportunity for patients to report their symptoms systematically, communicate these symptoms to cancer nurses and to receive self-care advice via an application in an Information and Communication Technology-platform could overcome this risk. The content in the application must precisely capture symptoms that are significant to both patients and health care professionals. Therefore, the aim of the study was to map and describe symptoms and self-care strategies identified by patients with prostate cancer undergoing radiotherapy, by health care professionals caring for these patients, and in the literature.

    Methods: The study combines data from interviews with patients (n ¼ 8) and health care professionals (n ¼ 10) and a scoping review of the literature (n ¼ 26) focusing on the period during and up to 6 months after radiotherapy.

    Results: There was a concordance between the patients, health care professionals, and the literature on symptoms during and after radiotherapy. Urinary symptoms, bowel problems, pain, sexual problems, fatigue, anxiety, depression, cognitive impairment and irregular symptoms were commonly described during the initial treatment period. Self-care strategies were rarely described in all three of the sources.

    Conclusions: The results show which symptoms to regularly assess using an Information and Communication Technology-platform for patients with newly-diagnosed prostate cancer during radiotherapy. The next step is to evaluate the efficacy of using the platform and the accuracy of the selected symptoms and self-care advice included in a smartphone application.

  • 38.
    Bohr Mordhorst, Louise
    et al.
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Örebro University Hospital. Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Prognostic impact of the expression of Hedgehog proteins in cervical carcinoma FIGO stages I-IV treated with radiotherapy or chemoradiotherapy2014In: Gynecologic Oncology, ISSN 0090-8258, E-ISSN 1095-6859, Vol. 135, no 2, p. 305-311Article in journal (Refereed)
    Abstract [en]

    Objective: Hedgehog signaling proteins were assessed in patients with cervical carcinoma receiving chemoradiation. Associations between five Hedgehog proteins and prognosis were studied.

    Methods: In all, 131 cases of cervical carcinomas (FIGO stages I-IV) were immunohistochemically (IHC) analyzed for Patched (PTCH), Smoothened (SMO), and GLI1, GLI2 and GLI3 protein expression. Associations between Hedgehog protein expressions, clinicopathological factors, and clinical outcome data were examined.

    Results: Positive IHC staining for the five Hedgehog proteins was recorded in 8% to 37% of the tumor cells. The highest frequency was noted for SMO and the lowest for all. There was a significant association between low SMO- and GLI2-expression and KRAS-mutation. Tumors with overexpressed SMO had a higher frequency of residual tumor or local recurrences than tumors with low SMO expression. Patients with tumors expressing PTCH in more than 75% of the cells had significantly (P = 0.023) better recurrence-free survival than patients with tumors with low expression. The opposite situation was true for SMO. For GLI2, there was a statistically significant difference with regard to overall (P = 0.004) and distant (P = 0.015) relapse rate for groups with expression of GLI2 in the range of 5-25% compared to higher rates.

    Conclusions: A predictive and prognostic value was found for PTCH, SMO, and GLI2 with regard to residual carcinoma, local recurrences, and for GLI2 distant relapses. The Hedgehog signaling pathway also seems to play an important role in cervical carcinogenesis together with HPV16-infection and KRAS-mutation.

  • 39.
    Bohr Mordhorst, Louise
    et al.
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Sorbe, Bengt
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy2016In: OncoTarget, ISSN 1949-2553, E-ISSN 1949-2553, Vol. 7, no 39, p. 63042-63053Article in journal (Refereed)
    Abstract [en]

    Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for β-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the β-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between β-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear β-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for β-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.

  • 40.
    Bohr Mordhorst, Louise
    et al.
    Örebro University Hospital.
    Sorbe, Bengt
    Örebro University Hospital.
    Ahlin, Cecilia
    Department of Oncology, Örebro University Hospital, Örebro, Sweden.
    A study of serum biomarkers associated with relapse of cervical cancer2012In: Anticancer Research, ISSN 0250-7005, E-ISSN 1791-7530, Vol. 32, no 11, p. 4913-22Article in journal (Refereed)
    Abstract [en]

    BACKGROUND/AIM: To discover candidate protein biomarkers in the serum of patients with cervical cancer that differentiate between patients with relapse from those who are tumor-free after primary treatment with (platinum-based chemo-) radiation.

    PATIENTS AND METHODS: Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF-MS) with cation exchange (CM10) and hydrophobic/reverse-phase (H50) was used to examine 44 serum samples from patients with advanced cervical cancer, primarily treated with (platinum-based chemo-) radiation.

    RESULTS: Ten candidate biomarkers were identified in the serum of 34 patients. Six candidate markers were elevated in patients with no relapse and four were elevated in patients with relapse [p=0.007-0.11; area under the curve (AUC)=0.70-0.75]. Masses of candidate biomarkers ranged from 2,022 to 116,165 Da.

    CONCLUSION: Patients with relapse from primary advanced cervical cancer exhibit different serum protein expression profiles from those with no relapse.

  • 41.
    Borgquist, Signe
    et al.
    Dept Clin Sci, Div Oncol & Pathol, Lund Univ, Lund, Sweden.
    Zhou, Wenjing
    Dept Surg Sci, Uppsala Univ, Uppsala, Sweden.
    Jirstrom, Karin
    Dept Clin Sci, Div Oncol & Pathol, Lund Univ, Lund, Sweden.
    Amini, Rose-Marie
    Dept Genet & Pathol, Uppsala Univ, Uppsala, Sweden.
    Sollie, Thomas
    Dept Pathol, Örebro University Hospital, Örebro, Sweden.
    Sorlie, Therese
    Norwegian Radium Hosp, Inst Canc Res, Dept Genet, Oslo Univ Hosp, Oslo, Norway.
    Blomqvist, Carl
    Cent Hosp, Dept Oncol, Univ Helsinki, Helsinki, Finland.
    Butt, Salma
    Dept Surg, Lund Univ, Malmö, Sweden.
    Warnberg, Fredrik
    Dept Surg Sci, Uppsala Univ, Uppsala, Sweden.
    The prognostic role of HER2 expression in ductal breast carcinoma in situ (DCIS); a population-based cohort study2015In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 15, article id 468Article in journal (Refereed)
    Abstract [en]

    Background: HER2 is a well-established prognostic and predictive factor in invasive breast cancer. The role of HER2 in ductal breast carcinoma in situ (DCIS) is debated and recent data have suggested that HER2 is mainly related to in situ recurrences. Our aim was to study HER2 as a prognostic factor in a large population based cohort of DCIS with long-term follow-up. Methods: All 458 patients diagnosed with a primary DCIS 1986-2004 in two Swedish counties were included. Silver-enhanced in situ hybridisation (SISH) was used for detection of HER2 gene amplification and protein expression was assessed by immunohistochemistry (IHC) in tissue microarrays. HER2 positivity was defined as amplified HER2 gene and/or HER2 3+ by IHC. HER2 status in relation to new ipsilateral events (IBE) and Invasive Breast Cancer Recurrences, local or distant (IBCR) was assessed by Kaplan-Meier survival analyses and Cox proportional hazards regression models. Results: Primary DCIS was screening-detected in 75.5 % of cases. Breast conserving surgery (BCS) was performed in 78.6 % of whom 44.0 % received postoperative radiotherapy. No patients received adjuvant endocrine-or chemotherapy. The majority of DCIS could be HER2 classified (N = 420 (91.7 %)); 132 HER2 positive (31 %) and 288 HER2 negative (69 %)). HER2 positivity was related to large tumor size (P = 0.002), high grade (P < 0.001) and ER-and PR negativity (P < 0.001 for both). During follow-up (mean 184 months), 106 IBCRs and 105 IBEs were identified among all 458 cases corresponding to 54 in situ and 51 invasive recurrences. Eighteen women died from breast cancer and another 114 had died from other causes. The risk of IBCR was statistically significantly lower subsequent to a HER2 positive DCIS compared to a HER2 negative DCIS, (Log-Rank P = 0.03, (HR) 0.60 (95 % CI 0.38-0.94)). Remarkably, the curves did not separate until after 10 years. In ER-stratified analyses, HER2 positive DCIS was associated with lower risk of IBCR among women with ER negative DCIS (Log-Rank P = 0.003), but not for women with ER positive DCIS. Conclusions: Improved prognostic tools for DCIS patients are warranted to tailor adjuvant therapy. Here, we demonstrate that HER2 positive disease in the primary DCIS is associated with lower risk of recurrent invasive breast cancer.

  • 42.
    Bostrom, Petrus
    et al.
    Department of Surgery and Perioperative Sciences, Umeå University Hospital, Umeå, Sweden.
    Rutegard, Jorgen
    Department of Surgery and Perioperative Sciences, Umeå University Hospital, Umeå, Sweden.
    Haapamaki, Markku
    Department of Surgery and Perioperative Sciences, Umeå University Hospital, Umeå, Sweden.
    Matthiessen, Peter
    Örebro University Hospital. Department of Surgery, Örebro University Hospital, Örebro, Sweden.
    Rutegard, Martin
    Department of Surgery and Perioperative Sciences, Umeå University Hospital, Umeå, Sweden; Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
    Arterial ligation in anterior resection for rectal cancer: A validation study of the Swedish Colorectal Cancer Registry2014In: Acta Oncologica, ISSN 0284-186X, E-ISSN 1651-226X, Vol. 53, no 7, p. 892-897Article in journal (Refereed)
    Abstract [en]

    Background: The level of arterial ligation has been a variable of the Swedish Colorectal Cancer Registry since 2007. The aim of this study is to evaluate the accuracy of this registry variable in relation to anterior resection for rectal cancer.

    Methods: The operative charts of all cardiovascularly compromised patients who underwent anterior resection during the period 2007-2010 in Sweden were retrieved and compared to the registry. We selected the study population to reflect the common assumption that these patients would be more sensitive to a compromised visceral blood flow. Levels of vascular ligation were defined, both oncologically and functionally, and their sensitivity, specificity, positive and negative predictive values, level of agreement and Cohen's kappa were calculated.

    Results: Some 744 (94.5%) patients were eligible for analysis. Functional high tie level showed a sensitivity of 80.2% and a specificity of 90.1%. Positive and negative predictive values were 87.7 and 83.8%, respectively. Level of agreement was 85.5% and Cohen's kappa 0.70. The corresponding calculations for oncologic tie level yielded similar results.

    Conclusion: The suboptimal validity of the Swedish Colorectal Cancer Registry regarding the level of vascular ligation might be problematic. For analyses with rare positive outcomes, such bowel ischaemia, or with minor expected differences in outcomes, it would be beneficial to collect data directly from the operative charts of the medical records in order to increase the chance of identifying clinically relevant differences.

  • 43.
    Botling, Johan
    et al.
    Departments of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Edlund, Karolina
    Departments of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Lohr, Miriam
    Department of Statistics, TU Dortmund University, Dortmund, Germany.
    Hellwig, Birte
    Department of Statistics, TU Dortmund University, Dortmund, Germany.
    Holmberg, Lars
    Dept. Surgical Sciences, Uppsala University, Uppsala, Sweden; Regional Cancer Center Uppsala Örebro, Akademiska sjukhuset, Uppsala, Sweden; Division of Cancer Studies, King's College Medical School, London, United Kingdom.
    Lambe, Mats G.
    Regional Cancer Center Uppsala Örebro, Akademiska sjukhuset, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Berglund, Anders
    Regional Cancer Center Uppsala Örebro, Akademiska sjukhuset, Uppsala, Sweden; Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
    Ekman, Simon
    Radiology, Oncology and Radiation Sciences, Section of Oncology, Uppsala University, Uppsala, Sweden.
    Bergqvist, Michael
    Radiology, Oncology and Radiation Sciences, Section of Oncology, Uppsala University, Uppsala, Sweden.
    Pontén, Fredrik
    Departments of 1Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    König, André
    Department of Statistics, TU Dortmund University, Dortmund, Germany.
    Fernandes, Oswaldo
    Cardiothoracic Surgery, Örebro University Hospital, Örebro, Sweden.
    Karlsson, Mats
    Örebro University Hospital. Laboratory Medicine.
    Helenius, Gisela
    Örebro University Hospital. Laboratory Medicine.
    Karlsson, Christina
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
    Rahnenfuehrer, Jörg
    Department of Statistics, TU Dortmund University, Dortmund, Germany.
    Hengstler, Jan G.
    Leibniz Research Centre for Working Environment and Human Factors (IfADo), Dortmund, Germany.
    Micke, Patrick
    Departments of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
    Biomarker Discovery in Non-Small Cell Lung Cancer: Integrating Gene Expression Profiling, Meta-analysis, and Tissue Microarray Validation2013In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 19, no 1, p. 194-204Article in journal (Refereed)
    Abstract [en]

    Purpose: Global gene expression profiling has been widely used in lung cancer research to identify clinically relevant molecular subtypes as well as to predict prognosis and therapy response. So far, the value of these multigene signatures in clinical practice is unclear, and the biologic importance of individual genes is difficult to assess, as the published signatures virtually do not overlap.

    Experimental Design: Here, we describe a novel single institute cohort, including 196 non-small lung cancers (NSCLC) with clinical information and long-term follow-up. Gene expression array data were used as a training set to screen for single genes with prognostic impact. The top 450 probe sets identified using a univariate Cox regression model (significance level P < 0.01) were tested in a meta-analysis including five publicly available independent lung cancer cohorts (n = 860).

    Results: The meta-analysis revealed 14 genes that were significantly associated with survival (P < 0.001) with a false discovery rate < 1%. The prognostic impact of one of these genes, the cell adhesion molecule 1 (CADM1), was confirmed by use of immunohistochemistry on tissue microarrays from 2 independent NSCLC cohorts, altogether including 617 NSCLC samples. Low CADM1 protein expression was significantly associated with shorter survival, with particular influence in the adenocarcinoma patient subgroup.

    Conclusions: Using a novel NSCLC cohort together with a meta-analysis validation approach, we have identified a set of single genes with independent prognostic impact. One of these genes, CADM1, was further established as an immunohistochemical marker with a potential application in clinical diagnostics. Clin Cancer Res; 19(1); 194-204. (c) 2012 AACR.

  • 44.
    Braegelmann, Johannes
    et al.
    Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany; Department of Hematology, Oncology and Rheumatology, University Hospital of Bonn, Bonn, Germany.
    Kluemper, Niklas
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Offermann, Anne
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Von Maessenhausen, Anne
    Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
    Böhm, Diana
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Deng, Mario
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Queisser, Angela
    Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
    Sanders, Christine
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Syring, Isabella
    Section for Prostate Cancer Research, University Hospital of Bonn, Bonn, Germany; Institute of Pathology, University Hospital of Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany; Clinic for Urology and Pediatric Urology, University Hospital of Bonn, Bonn, Germany.
    Merseburger, Axel S.
    Department of Urology, University Hospital Schleswig-Holstein, Lübeck, Germany.
    Vogel, Wenzel
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Sievers, Elisabeth
    Institute of Pathology, University Hospital of Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
    Vlasic, Ignacija
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology, Örebro University Hospital, Örebro, Sweden.
    Brossart, Peter
    Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany; Department of Hematology, Oncology and Rheumatology, University Hospital of Bonn, Bonn, Germany.
    Duensing, Stefan
    Molecular Uro-oncology, Department of Urology, University of Heidelberg, Heidelberg, Germany.
    Svensson, Maria A.
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Research and Education, Örebro University Hospital, Örebro, Sweden.
    Shaikhibrahim, Zaki
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Kirfel, Jutta
    Institute of Pathology, University Hospital of Bonn, Bonn, Germany; Center for Integrated Oncology Cologne/Bonn, University Hospital of Bonn, Bonn, Germany.
    Perner, Sven
    Pathology, University Medical Center Schleswig-Holstein, Lübeck, Germany; Research Center Borstel, Leibniz Center for Medicine and Biosciences, Borstel, Germany.
    Pan-Cancer Analysis of the Mediator Complex Transcriptome Identifies CDK19 and CDK8 as Therapeutic Targets in Advanced Prostate Cancer2017In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 23, no 7, p. 1829-1840Article in journal (Refereed)
    Abstract [en]

    Purpose: The Mediator complex is a multiprotein assembly, which serves as a hub for diverse signaling pathways to regulate gene expression. Because gene expression is frequently altered in cancer, a systematic understanding of the Mediator complex in malignancies could foster the development of novel targeted therapeutic approaches.

    Experimental Design: We performed a systematic deconvolution of the Mediator subunit expression profiles across 23 cancer entities (n = 8,568) using data from The Cancer Genome Atlas (TCGA). Prostate cancer-specific findings were validated in two publicly available gene expression cohorts and a large cohort of primary and advanced prostate cancer (n = 622) stained by immunohistochemistry. The role of CDK19 and CDK8 was evaluated by siRNA-mediated gene knockdown and inhibitor treatment in prostate cancer cell lines with functional assays and gene expression analysis by RNAseq.

    Results: Cluster analysis of TCGA expression data segregated tumor entities, indicating tumor-type-specific Mediator complex compositions. Only prostate cancerwasmarked by high expression of CDK19. In primary prostate cancer, CDK19 was associated with increased aggressiveness and shorter disease-free survival. During cancer progression, highest levels of CDK19 and of its paralog CDK8were present inmetastases. In vitro, inhibition ofCDK19 and CDK8 by knockdown or treatment with a selective CDK8/ CDK19 inhibitor significantly decreased migration and invasion.

    Conclusions: Our analysis revealed distinct transcriptional expression profiles of the Mediator complex across cancer entities indicating differential modes of transcriptional regulation. Moreover, it identified CDK19 and CDK8 to be specifically overexpressed during prostate cancer progression, highlighting their potential as novel therapeutic targets in advanced prostate cancer.

  • 45.
    Broberg, Gudrun
    et al.
    Department of Obstetrics and Gynaecology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg (Sweden); The Regional Cancer Centre, Western Health Care Region, Gothenburg, Sweden; Närhälsan Primary Care, Western Health Care Region, Skövde, Sweden .
    Jiangrong, Wang
    Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.
    Östberg, Anna-Lena
    Public Dental Service, Region Västra Götaland, Vänersborg, Sweden; Department of Behavioural and Community Dentistry, Institute of Odontology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden .
    Adolfsson, Annsofie
    Örebro University, School of Health Sciences. The Centre for Women’s, Family and Child Health, Faculty of Health Sciences, Buskerud & Vestfold University College, Kongsberg, Norway .
    Szilard, Nemes
    The Regional Cancer Centre, Western Health Care Region, Gothenburg, Sweden; Swedish Hip Arthroplasty Register, Gothenburg, Sweden.
    Björn, Strander
    Department of Obstetrics and Gynaecology, Institute of Clinical Science, Sahlgrenska Academy, University of Gothenburg /The Regional Cancer Centre, Western Health Care Region, Gothenburg, Sweden.
    Socio-economic and demographic determinants affecting participation in the Swedish cervical screening program: A population-based case-control study2018In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 13, no 1, article id e0190171Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Cervical screening programs are highly protective for cervical cancer, but only for women attending screening procedure.

    OBJECTIVE: Identify socio-economic and demographic determinants for non-attendance in cervical screening.

    METHODS: Design: Population-based case-control study. Setting: Sweden. Population: Source population was all women eligible for screening. Based on complete screening records, two groups of women aged 30-60 were compared. The case group, non-attending women, (N = 314,302) had no smear registered for 6-8 years. The control group (N = 266,706) attended within 90 days of invitation. Main outcome measures: Risk of non-attendance by 9 groups of socioeconomic and demographic variables. Analysis: Unadjusted odds ratios (OR) and OR after adjustment for all variables in logistic regression models were calculated.

    RESULTS: Women with low disposable family income (adjOR 2.06; 95% confidence interval (CI) 2.01-2.11), with low education (adjOR 1.77; CI 1.73-1.81) and not cohabiting (adjOR 1.47; CI 1.45-1.50) were more likely to not attend cervical screening. Other important factors for non-attendance were being outside the labour force and receiving welfare benefits. Swedish counties are responsible for running screening programs; adjusted OR for non-participation in counties ranged from OR 4.21 (CI 4.06-4.35) to OR 0.54 (CI 0.52-0.57), compared to the reference county. Being born outside Sweden was a risk factor for non-attendance in the unadjusted analysis but this disappeared in certain large groups after adjustment for socioeconomic factors.

    CONCLUSION: County of residence and socio-economic factors were strongly associated with lower attendance in cervical screening, while being born in another country was of less importance. This indicates considerable potential for improvement of cervical screening attendance in several areas if best practice of routines is adopted.

  • 46.
    Brocki, Barbara Cristina
    et al.
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Department of Occupational Therapy and Physiotherapy, Aalborg University Hospital, Aalborg, Denmark.
    Andreasen, Jane
    Department of Occupational Therapy and Physiotherapy, Aalborg University Hospital, Aalborg, Denmark.
    Nielsen, Lene Rodkjaer
    Department of Cardiothoracic Surgery, Aalborg University Hospital, Aalborg, Denmark.
    Nekrasas, Vytautas
    Department of Cardiothoracic Surgery, Aalborg University Hospital, Aalborg, Denmark.
    Gorst- Rasmussen, Anders
    Centre for Cardiovascular Research, Department of Cardiothoracic Surgery, Aalborg University Hospital, Aalborg, Denmark.
    Westerdahl, Elisabeth
    Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. Örebro University Hospital. Department of Physiotherapy, Örebro University Hospital, Örebro, Sweden.
    Short and long-term effects of supervised versus unsupervised exercise training on health-related quality of life and functional outcomes following lung cancer surgery: a randomized controlled trial2014In: Lung Cancer, ISSN 0169-5002, E-ISSN 1872-8332, Vol. 83, no 1, p. 102-108Article in journal (Refereed)
    Abstract [en]

    OBJECTIVE:

    Surgical resection enhances long-term survival after lung cancer, but survivors face functional deficits and report on poor quality of life long time after surgery. This study evaluated short and long-term effects of supervised group exercise training on health-related quality of life and physical performance in patients, who were radically operated for lung cancer.

    METHODS:

    A randomized, assessor-blinded, controlled trial was performed on 78 patients undergoing lung cancer surgery. The intervention group (IG, n=41) participated in supervised out-patient exercise training sessions, one hour once a week for ten weeks. The sessions were based on aerobic exercises with target intensity of 60-80% of work capacity, resistance training and dyspnoea management. The control group (CG, n=37) received one individual instruction in exercise training. Measurements consisted of: health-related quality of life (SF36), six minute walk test (6MWT) and lung function (spirometry), assessed three weeks after surgery and after four and twelve months.

    RESULTS:

    Both groups were comparable at baseline on demographic characteristic and outcome values. We found a statistically significant effect after four months in the bodily pain domain of SF36, with an estimated mean difference (EMD) of 15.3 (95% CI:4 to 26.6, p=0.01) and a trend in favour of the intervention for role physical functioning (EMD 12.04, 95% CI: -1 to 25.1, p=0.07) and physical component summary (EMD 3.76, 95% CI:-0.1 to 7.6, p=0.06). At 12 months, the tendency was reversed, with the CG presenting overall slightly better measures. We found no effect of the intervention on 6MWT or lung volumes at any time-point.

    CONCLUSION:

    Supervised compared to unsupervised exercise training resulted in no improvement in health-related quality of life, except for the bodily pain domain, four months after lung cancer surgery. No effects of the intervention were found for any outcome after one year.

  • 47.
    Brockmöller, Scarlet F.
    et al.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Bucher, Elmar
    Medical Biotechnology, VTT Technical Research Centre of Finland, University of Turku, Turku, Finland.
    Müller, Berit M.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Budczies, Jan
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Griffin, Julian L.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Kallioniemi, Olli
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Iljin, Kristiina
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Loibl, Sibylle
    German Breast Group, GBG-Forschungs GmbH, Neu-Isenburg, Germany.
    Darb-Esfahani, Silvia
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Sinn, Bruno V.
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Klauschen, Frederick
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Prinzler, Judith
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Bangemann, Nikola
    Breast Cancer Center, Charité University Hospital, Berlin, Germany.
    Ismaeel, Fakher
    Department of Gynaecology and Obstetrics, DRK Kliniken Köpenick, Berlin, Germany; Department of Gynaecology and Obstetrics, Charité University Hospital, Berlin, Germany.
    Fiehn, Oliver
    Genome Center, University of California-Davis, Davis CA, United States.
    Dietel, Manfred
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Denkert, Carsten
    Institute of Pathology, Charité- Universitätsmedizin Berlin, Berlin, Germany.
    Integration of metabolomics and expression of glycerol-3-phosphate acyltransferase (GPAM) in breast cancer-link to patient survival, hormone receptor status, and metabolic profiling2012In: Journal of Proteome Research, ISSN 1535-3893, E-ISSN 1535-3907, Vol. 11, no 2, p. 850-60Article in journal (Refereed)
    Abstract [en]

    Changes in lipid metabolism are an important but not well-characterized hallmark of cancer. On the basis of our recent findings of lipidomic changes in breast cancer, we investigated glycerol-3-phosphate acyltransferase (GPAM), a key enzyme in the lipid biosynthesis of triacylglycerols and phospholipids. GPAM protein expression was evaluated and linked to metabolomic and lipidomic profiles in a cohort of human breast carcinomas. In addition, GPAM mRNA expression was analyzed using the GeneSapiens in silico transcriptiomics database. High cytoplasmic GPAM expression was associated with hormone receptor negative status (p = 0.013). On the protein (p = 0.048) and mRNA (p = 0.001) levels, increased GPAM expression was associated with a better overall survival. Metabolomic analysis by GC-MS showed that sn-glycerol-3-phosphate, the substrate of GPAM, was elevated in breast cancer compared to normal breast tissue. LC-MS based lipidomic analysis identified significantly higher levels of phospholipids, especially phosphatidylcholines in GPAM protein positive tumors. In conclusion, our results suggest that GPAM is expressed in human breast cancer with associated changes in the cellular metabolism, in particular an increased synthesis of phospholipids, the major structural component of cellular membranes.

  • 48.
    Budczies, Jan
    et al.
    Institute of Pathology, Charité University Hospital, Berlin, Germany; German Cancer Consortium (DKTK), Heidelberg, Germany; German Cancer Research Center (DKFZ), Heidelberg, Germany.
    Brockmöller, Scarlet F.
    Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
    Müller, Berit M.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Barupal, Dinesh K.
    International Agency for Research on Cancer (IARC), Lyon, France.
    Richter-Ehrenstein, Christiane
    Interdisciplinary Breast Center, Charité University Hospital, Berlin, Germany.
    Kleine-Tebbe, Anke
    Breast Center, DRK Kliniken Berlin, Berlin, Germany.
    Griffin, Julian L.
    Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
    Oresic, Matej
    Örebro University, School of Medical Sciences. Department of Biochemistry and Cambridge Systems Biology Centre, University of Cambridge, Cambridge, United Kingdom.
    Dietel, Manfred
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Denkert, Carsten
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Fiehn, Oliver
    Genome Center, University of California Davis, Davis CA, United States.
    Comparative metabolomics of estrogen receptor positive and estrogen receptor negative breast cancer: alterations in glutamine and beta-alanine metabolism2013In: Journal of Proteomics, ISSN 1874-3919, E-ISSN 1876-7737, Vol. 94, p. 279-288, article id S1874-3919(13)00511-3Article in journal (Refereed)
    Abstract [en]

    UNLABELLED: Molecular subtyping of breast cancer is necessary for therapy selection and mandatory for all breast cancer patients. Metabolic alterations are considered a hallmark of cancer and several metabolic drugs are currently being investigated in clinical trials. However, the dependence of metabolic alterations on breast cancer subtypes has not been investigated on -omics scale. Thus, 204 estrogen receptor positive (ER+) and 67 estrogen receptor negative (ER-) breast cancer tissues were investigated using GC-TOFMS based metabolomics. 19 metabolites were detected as altered in a predefined training set (2/3 of tumors) and could be validated in a predefined validation set (1/3 of tumors). The metabolite changes included increases in beta-alanine, 2-hydroyglutarate, glutamate, xanthine and decreases in glutamine in the ER- subtype. Beta-alanine demonstrated the strongest change between ER- and ER+ breast cancer (fold change=2.4, p=1.5E-20). In a correlation analysis with genome-wide expression data in a subcohort of 154 tumors, we found a strong negative correlation (Spearman R=-0.62) between beta-alanine and 4-aminobutyrate aminotransferase (ABAT). Immunohistological analysis confirmed down-regulation of the ABAT protein in ER- breast cancer. In a Kaplan-Meier analysis of a large external expression data set, the ABAT transcript was demonstrated to be a positive prognostic marker for breast cancer (HR=0.6, p=3.2E-15).

    BIOLOGICAL SIGNIFICANCE: It is well-known for more than a decade that breast cancer exhibits distinct gene expression patterns depending on the molecular subtype defined by estrogen receptor (ER) and HER2 status. Here, we show that breast cancer exhibits distinct metabolomics patterns depending on ER status. Our observation supports the current view of ER+ breast cancer and ER- breast as different diseases requiring different treatment strategies. Metabolic drugs for cancer including glutaminase inhibitors are currently under development and tested in clinical trials. We found glutamate enriched and glutamine reduced in ER- breast cancer compared to ER+ breast cancer and compared to normal breast tissues. Thus, metabolomics analysis highlights the ER- subtype as a preferential target for glutaminase inhibitors. For the first time, we report on a regulation of beta-alanine catabolism in cancer. In breast cancer, ABAT transcript expression was variable and correlated with ER status. Low ABAT transcript expression was associated with low ABAT protein expression and high beta-alanine concentration. In a large external microarray cohort, low ABAT expression shortened recurrence-free survival in breast cancer, ER+ breast cancer and ER- breast cancer.

  • 49.
    Budczies, Jan
    et al.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Denkert, Carsten
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Müller, Berit M.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Brockmöller, Scarlet F.
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Klauschen, Frederick
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Györffy, Balazs
    Institute of Pathology, Charité University Hospital, Berlin, Germany; Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Dietel, Manfred
    Institute of Pathology, Charité University Hospital, Berlin, Germany.
    Richter-Ehrenstein, Christiane
    Interdisciplinary Breast Center, Charité University Hospital, Berlin, Germany.
    Marten, Ulrike
    Institute of Pathology, DRK Kliniken Berlin, Berlin, Germany.
    Salek, Reza M.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Griffin, Julian L.
    Department of Biochemistry, University of Cambridge, Cambridge, United Kingdom.
    Hilvo, Mika
    VTT Technical Research Centre of Finland, Espoo, Finland.
    Oresic, Matej
    Örebro University, School of Medical Sciences. VTT Technical Research Centre of Finland, Espoo, Finland.
    Wohlgemuth, Gert
    Genome Center, University of California Davis, Davis CA, United States.
    Fiehn, Oliver
    Genome Center, University of California Davis, Davis CA, United States.
    Remodeling of central metabolism in invasive breast cancer compared to normal breast tissue - a GC-TOFMS based metabolomics study2012In: BMC Genomics, ISSN 1471-2164, E-ISSN 1471-2164, Vol. 13, no 1, article id 334Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Changes in energy metabolism of the cells are common to many kinds of tumors and are considered a hallmark of cancer. Gas chromatography followed by time-of-flight mass spectrometry (GC-TOFMS) is a well-suited technique to investigate the small molecules in the central metabolic pathways. However, the metabolic changes between invasive carcinoma and normal breast tissues were not investigated in a large cohort of breast cancer samples so far.

    RESULTS: A cohort of 271 breast cancer and 98 normal tissue samples was investigated using GC-TOFMS-based metabolomics. A total number of 468 metabolite peaks could be detected; out of these 368 (79%) were significantly changed between cancer and normal tissues (p<0.05 in training and validation set). Furthermore, 13 tumor and 7 normal tissue markers were identified that separated cancer from normal tissues with a sensitivity and a specificity of >80%. Two-metabolite classifiers, constructed as ratios of the tumor and normal tissues markers, separated cancer from normal tissues with high sensitivity and specificity. Specifically, the cytidine-5-monophosphate / pentadecanoic acid metabolic ratio was the most significant discriminator between cancer and normal tissues and allowed detection of cancer with a sensitivity of 94.8% and a specificity of 93.9%.

    CONCLUSIONS: For the first time, a comprehensive metabolic map of breast cancer was constructed by GC-TOF analysis of a large cohort of breast cancer and normal tissues. Furthermore, our results demonstrate that spectrometry-based approaches have the potential to contribute to the analysis of biopsies or clinical tissue samples complementary to histopathology.

  • 50.
    Bugaytsova, Jeanna A.
    et al.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Björnham, Oscar
    Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden; Swedish Defence Research Agency, Umeå, Sweden.
    Chernov, Yevgen A.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Gideonsson, Pär
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Henriksson, Sara
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; Umeå Core Facil Electron Microscopy UCEM, Umeå University, Umeå, Sweden.
    Mendez, Melissa
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Sjöström, Rolf
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Mahdavi, Jafar
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; School of Life Sciences, CBS, University of Nottingham, Nottingham, United Kingdom.
    Shevtsova, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Ilver, Dag
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; Acreo Swedish ICT AB, Gothenburg, Sweden.
    Moonens, Kristof
    Structural and Molecular Microbiology, VIB Department of Structural Biology, Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium .
    Quintana-Hayashi, Macarena P.
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Moskalenko, Roman
    Department of Pathology, Medical Institute, Sumy State University, Sumy, Ukraine.
    Aisenbrey, Christopher
    Department of Chemistry, Umeå University, Umeå, Sweden; Inst Chim, Univ Strasbourg, Strasbourg, France.
    Bylund, Göran
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Schmidt, Alexej
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden; Dept Med Biosci, Umeå Univ, Umeå, Sweden.
    Åberg, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Brännström, Kristoffer
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Königer, Verena
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
    Vikström, Susanne
    Department of Medical Biochemistry and Biophysics & Faculty Science and Technology, Umeå University, Umeå, Sweden.
    Rakhimova, Lena
    Department of Chemistry, Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Hofer, Anders
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Ögren, Johan
    Department of Odontology, Umeå University, Umeå, Sweden.
    Liu, Hui
    Department of Medicine, USUHS, Bethesda MD, United States.
    Goldman, Matthew D.
    Department of Pediatrics, USUHS, Bethesda MD, United States.
    Whitmire, Jeannette M.
    Department of Microbiology and Immunology, USUHS, Bethesda MD, United States.
    Ådén, Jörgen
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Younson, Justine
    Dental Institute, King's College London, London, United Kingdom.
    Kelly, Charles G.
    Dental Institute, King's College London, London, United Kingdom.
    Gilman, Robert H.
    Department of International Health, John Hopkins School of Public Health, Baltimore MD, United States.
    Chowdhury, Abhijit
    Centre for Liver Research, School of Digestive and Liver Diseases, Institute of Post Graduate Medical Education & Research, Kolkata, India.
    Mukhopadhyay, Asish K.
    Division of Bacteriology, National Institute of Cholera and Enteric Diseases, Kolkata, India.
    Nair, G. Balakrish
    Translational Health Science and Technology Institute, Haryana, India; WHO Research Policy & Cooperation Unit, New Delhi, India.
    Papadakos, Konstantinos S.
    Hellenic Pasteur Institute, Athens, Greece; Department of Translational Medicine, Wallenberg Lab, Lund University, Malmö, Sweden.
    Martinez-Gonzalez, Beatriz
    Hellenic Pasteur Institute, Athens, Greece.
    Sgouras, Dionyssios N.
    Hellenic Pasteur Institute, Athens, Greece.
    Engstrand, Lars
    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden; Sci Life Lab, Solna, Sweden.
    Unemo, Magnus
    Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Danielsson, Dan
    Örebro University Hospital. Department of Laboratory Medicine, Microbiology, Örebro University Hospital, Örebro, Sweden.
    Suerbaum, Sebastian
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany ; Institute of Medical Microbiology and Hospital Epidemiology, Hannover Medical School, Hannover, Germany; German Center for Infection Research (DZIF), Hannover, Germany; German Center for Infection Research (DZIF), Munich, Germany.
    Oscarson, Stefan
    Centre for Synthesis and Chemical Biology, School of Chemistry, University College Dublin, Dublin, Ireland.
    Morozova-Roche, Ludmilla A.
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Olofsson, Anders
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Gröbner, Gerhard
    Department of Chemistry, Umeå University, Umeå, Sweden.
    Holgersson, Jan
    Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska Academy, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden.
    Esberg, Anders
    Department of Odontology, Umeå University, Umeå, Sweden.
    Strömberg, Nicklas
    Department of Odontology, Umeå University, Umeå, Sweden.
    Landström, Maréne
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany.
    Eldridge, Angela M.
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento CA, United States; Genentech Inc, Vacaville CA, USA.
    Chromy, Brett A.
    Department of Pathology and Laboratory Medicine, University of California Davis School of Medicine, Sacramento CA, United States ; Singulex Inc, Alameda CA, USA.
    Hansen, Lori M.
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California Davis, Davis CA, United States.
    Solnick, Jay V.
    Departments of Medical Microbiology and Immunology, Center for Comparative Medicine, University of California, Davis CA, United States; California National Primate Research Center, University of California, Davis CA, USA .
    Lindén, Sara K.
    Department of Medical Biochemistry and Cell Biology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
    Haas, Rainer
    Max von Pettenkofer Institute of Hygiene and Medical Microbiology, LMU Munich, Munich, Germany; German Center for Infection Research (DZIF), Munich, Germany .
    Dubois, Andre
    Department of Medicine, Uniformed Services University of the Health Sciences, Bethesda MD, United States.
    Merrell, D. Scott
    Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda MD, United States.
    Schedin, Staffan
    Department of Applied Physics and Electronics, Umeå University, Umeå, Sweden.
    Remaut, Han
    Structural and Molecular Microbiology, VIB Department of Structural Biology, Brussels, Belgium; Structural Biology Brussels, Vrije Universiteit Brussel, Brussels, Belgium .
    Arnqvist, Anna
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Berg, Douglas E.
    Department of Medicine, University of California San Diego, La Jolla CA, United States.
    Borén, Thomas
    Department of Medical Biochemistry and Biophysics, Umeå University, Umeå, Sweden.
    Helicobacter pylori adapts to chronic infection and gastric disease via ph-responsive baba-mediated adherence2017In: Cell Host and Microbe, ISSN 1931-3128, E-ISSN 1934-6069, Vol. 21, no 3, p. 376-389, article id S1931-3128(17)30075-6Article in journal (Refereed)
    Abstract [en]

    The BabA adhesin mediates high-affinity binding of Helicobacter pylori to the ABO blood group antigen-glycosylated gastric mucosa. Here we show that BabA is acid responsive-binding is reduced at low pH and restored by acid neutralization. Acid responsiveness differs among strains; often correlates with different intragastric regions and evolves during chronic infection and disease progression; and depends on pH sensor sequences in BabA and on pH reversible formation of high-affinity binding BabA multimers. We propose that BabA's extraordinary reversible acid responsiveness enables tight mucosal bacterial adherence while also allowing an effective escape from epithelial cells and mucus that are shed into the acidic bactericidal lumen and that bio-selection and changes in BabA binding properties through mutation and recombination with babA-related genes are selected by differences among individuals and by changes in gastric acidity over time. These processes generate diverse H. pylori subpopulations, in which BabA's adaptive evolution contributes to H. pylori persistence and overt gastric disease.

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