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Appendicitis before age 20 years is associated with an increased risk of later prostate cancer
Örebro University, School of Medical Sciences. Department of Urology.
Örebro University, School of Medical Sciences. (Clinical Epidemiology and Biostatistics)
Örebro University, School of Medical Sciences. Örebro University Hospital. Department of Urology.ORCID iD: 0000-0001-5533-7899
Örebro University, School of Medical Sciences. Department of Urology.
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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. Vol. 27, no 6, p. 660-664
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:oru:diva-66449DOI: 10.1158/1055-9965.EPI-17-1204ISI: 000433945800006PubMedID: 29588305Scopus ID: 2-s2.0-85047896683OAI: oai:DiVA.org:oru-66449DiVA, id: diva2:1197681
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
In thesis
1. Inflammation and prostate carcinogenesis: influence of immune characteristics and early-adulthood exposure to inflammatory conditions on prostate cancer risk
Open this publication in new window or tab >>Inflammation and prostate carcinogenesis: influence of immune characteristics and early-adulthood exposure to inflammatory conditions on prostate cancer risk
2019 (English)Doctoral 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.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2019. p. 100
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 191
Keywords
Prostate cancer, inflammation, Cutibacterium acnes, acne, appendicitis, cytokines, circulating, inflammation marker, IL6, CXCL8
National Category
Surgery
Identifiers
urn:nbn:se:oru:diva-72812 (URN)978-91-7529-280-9 (ISBN)
Public defence
2019-05-10, Örebro universitet, Campus USÖ, hörsal C1, Södra Grev Rosengatan 32, Örebro, 12:30 (Swedish)
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Supervisors
Available from: 2019-02-27 Created: 2019-02-27 Last updated: 2019-04-10Bibliographically approved

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Ugge, HenrikUdumyan, RuzanCarlsson, JessicaDavidsson, SabinaAndrén, OveMontgomery, ScottFall, Katja

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