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  • 1.
    Ugge, Henrik
    Örebro University, School of Medical Sciences.
    Inflammation and prostate carcinogenesis: influence of immune characteristics and early-adulthood exposure to inflammatory conditions on prostate cancer risk2019Doctoral thesis, comprehensive summary (Other academic)
    Abstract [en]

    Chronic inflammation has been implicated in the development of several types of cancer, and evidence from observational and animal studies suggests that it may play a role also in prostate carcinogenesis. Recent observations have brought Cutibacterium acnes (C. acnes) forward as a possible causative agent in pro-oncogenic prostatic inflammation. However, evidence also suggest that underlying immune characteristics contribute to prostate cancer risk. The overall aim of this thesis was to explore potential mechanisms underlying the proposed link between inflammation and prostate cancer, by evaluating associations between inflammatory conditions during early adulthood, circulating inflammation markers, and prostate cancer. Due to the suggested role of C. acnes in both diseases, we aimed to investigate whether acne vulgaris is a determinant of prostate cancer. Using prospectively collected data from Swedish national registers, we observed that presence of acne during early adulthood conferred an increased risk of prostate cancer later in life. Similarly, we found that appendicitis before late adolescence – a proposed marker of individual immune characteristics – to be positively associated with subsequent prostate cancer. We further evaluated whether prostatic C. acnes infection is linked with elevated systemic levels of IL6 and CXCL8, two inflammation markers previously associated with prostate cancer. No association was observed, however, potentially explained by the subclinical low-grade infection typically caused by C. acnes. Finally, we evaluated 52 circulating inflammation markers as determinants for prostate cancer in a population-based case-control study. In this hypothesis-generating study, we identified CX3CL1, CCL21, PDGF-BB, CCL11 and IL10 as candidate markers for evaluation in prospective studies. If confirmed, these markers may hint at targetable molecular pathways involved in prostate carcinogenesis.

    List of papers
    1. Acne in late adolescence and risk of prostate cancer
    Open this publication in new window or tab >>Acne in late adolescence and risk of prostate cancer
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    2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, p. 1580-1585Article in journal (Refereed) Published
    Abstract [en]

    Accumulating evidence suggest that Propionibacterium acnes may play a role in prostate carcinogenesis, but data are so far limited and inconclusive. The aim of this population-based cohort study was therefore to test whether presence of acne vulgaris during late adolescence is associated with an increased risk of prostate cancer later in life. We identified a large cohort of young men born in Sweden between 1952 and 1956, who underwent mandatory assessment for military conscription around the age of 18 (n= 243,187). Test information along with health data including medical diagnoses at time of conscription was available through the Swedish Military Conscription Register and the National Patient Register. The cohort was followed through linkages to the Swedish Cancer Register to identify the occurrence of prostate cancer until December 31st 2009. We used Cox regression to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between acne in adolescence and prostate cancer risk. A total of 1,633 men were diagnosed with prostate cancer during a median follow-up of 36.7 years. A diagnosis of acne was associated with a statistically significant increased risk for prostate cancer (adjusted HR: 1.43 95%; CI: 1.06-1.92), particularly for advanced stage disease (HR: 2.37 95%; CI 1.19-4.73). A diagnosis of acne classified as severe conferred a 6-fold increased risk of prostate cancer (HR: 5.70 95% CI 1.42-22.85). Data from this large prospective population-based cohort add new evidence supporting a role of P acnes infection in prostate cancer.

    Place, publisher, year, edition, pages
    Hoboken, NJ, USA: John Wiley & Sons, 2018
    Keywords
    Propionibacterium acnes; prostate cancer; acne vulgaris; inflammation; acne vulgaris
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:oru:diva-63302 (URN)10.1002/ijc.31192 (DOI)000425184800009 ()29205339 (PubMedID)2-s2.0-85037982996 (Scopus ID)
    Note

    Funding Agency:

    UK Economic and Social Research Council (ESRC)  RES-596-28-0001  ES/JO19119/1

    Available from: 2017-12-11 Created: 2017-12-11 Last updated: 2019-04-09Bibliographically approved
    2. The influence of prostatic Cutibacterium acnes infection on serum levels of IL6 and CXCL8 in prostate cancer patients
    Open this publication in new window or tab >>The influence of prostatic Cutibacterium acnes infection on serum levels of IL6 and CXCL8 in prostate cancer patients
    Show others...
    2018 (English)In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 13, article id 34Article in journal (Refereed) Published
    Abstract [en]

    Background: Chronic prostatic inflammation, caused by Cutibacterium acnes (C. acnes), has been proposed to influence the risk of prostate cancer development. In vitro studies have demonstrated the capacity of C. acnes to induce secretion of Interleukin 6 (IL6) and C-X-C motif chemokine ligand 8 (CXCL8) by prostate epithelial cells. Both these inflammatory mediators have been implicated in prostate cancer pathophysiology. In this cohort study, we aimed to investigate the influence of prostatic C. acnes on serum levels of IL6 and CXCL8.

    Methods: We recruited 99 prostate cancer patients who underwent radical prostatectomy at orebro University Hospital. The cultivation of pre-operatively obtained prostate biopsies identified C. acnes in 60 of the 99 patients. Levels of IL6 and CXCL8 in pre-operative serum samples were analyzed using ELISA, and concentrations were compared between prostate cancer patients with and without prostatic C. acnes infection using standard statistical methods.

    Results: No statistical differences were observed in serum levels of IL6 and CXCL8 between subjects with and without prostatic C. acnes infection.

    Conclusions: Our results indicate that prostatic C. acnes infection may give rise to low-grade inflammation with little effect on systemic levels of IL6 and CXCL8.

    Place, publisher, year, edition, pages
    BioMed Central, 2018
    Keywords
    Prostate cancer, Inflammation, Cutibacterium acnes, IL6, CXCL8, Cytokines
    National Category
    Cancer and Oncology Immunology in the medical area
    Identifiers
    urn:nbn:se:oru:diva-70366 (URN)10.1186/s13027-018-0204-7 (DOI)000450287500001 ()30473726 (PubMedID)2-s2.0-85056906445 (Scopus ID)
    Note

    Funding Agency:

    Foundation Lions Cancerforskningsfond vid Akademiska sjukhuset i Uppsala 

    Available from: 2018-11-29 Created: 2018-11-29 Last updated: 2019-04-08Bibliographically approved
    3. Appendicitis before age 20 years is associated with an increased risk of later prostate cancer
    Open this publication in new window or tab >>Appendicitis before age 20 years is associated with an increased risk of later prostate cancer
    Show others...
    2018 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 27, no 6, p. 660-664Article in journal (Refereed) Published
    Abstract [en]

    BACKGROUND: Appendicitis before age 20 years has been observed to influence the risk of several inflammatory conditions, possibly through underlying immunological mechanisms. Inflammation has further been suggested to be involved in prostate cancer development. We therefore hypothesized that immunological characteristics signaled by appendicitis before late adolescence might influence the risk of later prostate cancer, and aimed to evaluate this association in a population-based study.

    METHODS: We identified a large cohort of Swedish men who underwent assessment for military conscription around the age of 18 years (n= 242,573). Medical diagnoses at time of conscription were available through the Swedish Military Conscription Register. The Swedish Cancer Register was used to identify diagnoses of prostate cancer. Multivariable adjusted Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between appendicitis and prostate cancer.

    RESULTS: During a median of 36.7 years of follow-up, 1,684 diagnoses of prostate cancer occurred. We found a statistically significant association between appendicitis and overall prostate cancer (adjusted HR: 1.70; 95% CI: 1.08-2.67). The risk was notably increased for advanced (HR: 4.42; 95% CI: 1.74-11.22) and lethal (HR: 8.95; 95% CI: 2.98-26.91) prostate cancer.

    CONCLUSION: These results suggest that a diagnosis of appendicitis before adulthood potentially signals underlying immune characteristics and a pattern of inflammatory response relevant to prostate cancer risk.

    IMPACT: The study lends support to the proposed role of inflammation in prostate carcinogenesis, and adds another area of investigation potentially relevant to prostate cancer development.

    Place, publisher, year, edition, pages
    American Association for Cancer Research, 2018
    National Category
    Cancer and Oncology
    Identifiers
    urn:nbn:se:oru:diva-66449 (URN)10.1158/1055-9965.EPI-17-1204 (DOI)000433945800006 ()29588305 (PubMedID)2-s2.0-85047896683 (Scopus ID)
    Note

    Funding Agency:

    UK Economic and Social Research Council (ESRC)  RES-596-28-0001  ES/JO19119/1

    Available from: 2018-04-13 Created: 2018-04-13 Last updated: 2019-04-09Bibliographically approved
    4. Circulating inflammation markers and prostate cancer
    Open this publication in new window or tab >>Circulating inflammation markers and prostate cancer
    Show others...
    (English)Manuscript (preprint) (Other academic)
    National Category
    Surgery
    Identifiers
    urn:nbn:se:oru:diva-73573 (URN)
    Available from: 2019-04-08 Created: 2019-04-08 Last updated: 2019-04-08Bibliographically approved
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  • 2.
    Ugge, Henrik
    et al.
    Örebro University, School of Medical Sciences. Department of Urology.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Department of Urology.
    Söderquist, Bo
    Örebro University, School of Medical Sciences.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology.
    The influence of prostatic Cutibacterium acnes infection on serum levels of IL6 and CXCL8 in prostate cancer patients2018In: Infectious Agents and Cancer, ISSN 1750-9378, E-ISSN 1750-9378, Vol. 13, article id 34Article in journal (Refereed)
    Abstract [en]

    Background: Chronic prostatic inflammation, caused by Cutibacterium acnes (C. acnes), has been proposed to influence the risk of prostate cancer development. In vitro studies have demonstrated the capacity of C. acnes to induce secretion of Interleukin 6 (IL6) and C-X-C motif chemokine ligand 8 (CXCL8) by prostate epithelial cells. Both these inflammatory mediators have been implicated in prostate cancer pathophysiology. In this cohort study, we aimed to investigate the influence of prostatic C. acnes on serum levels of IL6 and CXCL8.

    Methods: We recruited 99 prostate cancer patients who underwent radical prostatectomy at orebro University Hospital. The cultivation of pre-operatively obtained prostate biopsies identified C. acnes in 60 of the 99 patients. Levels of IL6 and CXCL8 in pre-operative serum samples were analyzed using ELISA, and concentrations were compared between prostate cancer patients with and without prostatic C. acnes infection using standard statistical methods.

    Results: No statistical differences were observed in serum levels of IL6 and CXCL8 between subjects with and without prostatic C. acnes infection.

    Conclusions: Our results indicate that prostatic C. acnes infection may give rise to low-grade inflammation with little effect on systemic levels of IL6 and CXCL8.

  • 3.
    Ugge, Henrik
    et al.
    Örebro University, School of Medical Sciences. Department of Urology.
    Downer, Mary K.
    Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, United States.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Bowden, Michaela
    Department of Medical Oncology, Dana–Farber Cancer Institute, Boston, United States.
    Davidsson, Sabina
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Mucci, Lorelai A.
    Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, United States.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Andersson, Sven-Olof
    Department of Urology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Circulating inflammation markers and prostate cancerManuscript (preprint) (Other academic)
  • 4.
    Ugge, Henrik
    et al.
    Örebro University, School of Medical Sciences. Department of Urology.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, UK.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology.
    Fall, Katja
    Örebro University, School of Medical Sciences. Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden.
    Acne in late adolescence and risk of prostate cancer2018In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, p. 1580-1585Article in journal (Refereed)
    Abstract [en]

    Accumulating evidence suggest that Propionibacterium acnes may play a role in prostate carcinogenesis, but data are so far limited and inconclusive. The aim of this population-based cohort study was therefore to test whether presence of acne vulgaris during late adolescence is associated with an increased risk of prostate cancer later in life. We identified a large cohort of young men born in Sweden between 1952 and 1956, who underwent mandatory assessment for military conscription around the age of 18 (n= 243,187). Test information along with health data including medical diagnoses at time of conscription was available through the Swedish Military Conscription Register and the National Patient Register. The cohort was followed through linkages to the Swedish Cancer Register to identify the occurrence of prostate cancer until December 31st 2009. We used Cox regression to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between acne in adolescence and prostate cancer risk. A total of 1,633 men were diagnosed with prostate cancer during a median follow-up of 36.7 years. A diagnosis of acne was associated with a statistically significant increased risk for prostate cancer (adjusted HR: 1.43 95%; CI: 1.06-1.92), particularly for advanced stage disease (HR: 2.37 95%; CI 1.19-4.73). A diagnosis of acne classified as severe conferred a 6-fold increased risk of prostate cancer (HR: 5.70 95% CI 1.42-22.85). Data from this large prospective population-based cohort add new evidence supporting a role of P acnes infection in prostate cancer.

  • 5.
    Ugge, Henrik
    et al.
    Örebro University, School of Medical Sciences. Department of Urology.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Carlsson, Jessica
    Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.
    Davidsson, Sabina
    Örebro University, School of Medical Sciences. Department of Urology.
    Andrén, Ove
    Örebro University, School of Medical Sciences. Department of Urology.
    Montgomery, Scott
    Örebro University, School of Medical Sciences. Clinical Epidemiology Unit, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Public Health, University College London, London, United Kingdom.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    Appendicitis before age 20 years is associated with an increased risk of later prostate cancer2018In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 27, no 6, p. 660-664Article in journal (Refereed)
    Abstract [en]

    BACKGROUND: Appendicitis before age 20 years has been observed to influence the risk of several inflammatory conditions, possibly through underlying immunological mechanisms. Inflammation has further been suggested to be involved in prostate cancer development. We therefore hypothesized that immunological characteristics signaled by appendicitis before late adolescence might influence the risk of later prostate cancer, and aimed to evaluate this association in a population-based study.

    METHODS: We identified a large cohort of Swedish men who underwent assessment for military conscription around the age of 18 years (n= 242,573). Medical diagnoses at time of conscription were available through the Swedish Military Conscription Register. The Swedish Cancer Register was used to identify diagnoses of prostate cancer. Multivariable adjusted Cox regression analyses were used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the association between appendicitis and prostate cancer.

    RESULTS: During a median of 36.7 years of follow-up, 1,684 diagnoses of prostate cancer occurred. We found a statistically significant association between appendicitis and overall prostate cancer (adjusted HR: 1.70; 95% CI: 1.08-2.67). The risk was notably increased for advanced (HR: 4.42; 95% CI: 1.74-11.22) and lethal (HR: 8.95; 95% CI: 2.98-26.91) prostate cancer.

    CONCLUSION: These results suggest that a diagnosis of appendicitis before adulthood potentially signals underlying immune characteristics and a pattern of inflammatory response relevant to prostate cancer risk.

    IMPACT: The study lends support to the proposed role of inflammation in prostate carcinogenesis, and adds another area of investigation potentially relevant to prostate cancer development.

  • 6.
    Ugge, Henrik
    et al.
    Örebro University, School of Medical Sciences. Department of Urology, Faculty of Health and Medical Sciences, Örebro University, Örebro, Sweden.
    Udumyan, Ruzan
    Örebro University, School of Medical Sciences.
    Montgomery, Scott
    Örebro University, School of Medical Sciences.
    Fall, Katja
    Örebro University, School of Medical Sciences.
    Asthma and allergy in adolescence and risk of prostate cancer2017In: Scandinavian journal of urology, ISSN 2168-1805, E-ISSN 2168-1813, Vol. 51, no Suppl. 220, p. 20-20Article in journal (Other academic)
    Abstract [en]

    Introduction: The role of inflammation in prostate cancer has been widely discussed [1]. Exploring the association between immunological or inflammatory conditions, that reflect immune response profile, and prostate cancer risk may provide clues to the type of inflammatory processes involved in the etiology of prostate cancer. Asthma and allergic conditions have been suggested to reduce the risk of prostate cancer, but data from large studies are currently scarce and results are conflicting [2,3].

    Objectives: To test if asthma, hay fever, or any allergic condition present in adolescence is associated with a decreased risk of prostate cancer later in life.

    Methods: This study is based on a cohort of 243,309 men born in Sweden between 1952 and 1956 who underwent mandatory conscription assessments for military service around ages 18-19 years. At this time, a thorough assessment of the men’s health was performed, and conditions such as asthma, hay fever, and allergies were recorded. The cohort was followed for incident prostate cancer through linkage with the Swedish cancer- and population registers. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between the selected conditions and prostate cancer incidence.

    Results: A total of 1,654 men were diagnosed with prostate cancer during a maximum of 40.3 years of follow-up (median 36.7 years). At the time of conscription assessment, there were 11,754 men with hay fever, 4,943 with an asthma-diagnosis and 16,112 with any allergic condition. We observed no difference in prostate cancer risk for men with asthma (HR: 0.91, 95% CI: 0.63-1.3), hay fever (HR: 1.03, 95% CI: 0.82-1.28) or any allergic condition (HR: 0.98, 95% CI: 0.8-1.19) compared with men without these diagnoses. Small numbers precluded separate analyses of men with advanced or lethal prostate cancer (n¼6 andn¼3, respectively).

    Conclusion: Our results do not support the hypothesis that presence of asthma or allergic conditions in late adolescence reduces the risk of prostate cancer later in life. If inflammatory processes are involved in the pathogenesis of prostate cancer, the immune response profiles likely differ from those reflected in clinical diagnoses of asthma or allergic conditions. The possibility that different risk patterns may be observed among older men with advanced or lethal prostate cancer, however, cannot be excluded.

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