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Circulating levels of testosterone, sex hormone binding globulin and colorectal cancer risk: Observational and mendelian randomization analyses
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.ORCID-id: 0000-0001-8540-6891
Umeå universitet, Medicinska fakulteten, Institutionen för strålningsvetenskaper, Onkologi.
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2021 (Engelska)Ingår i: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 30, nr 7, s. 1336-1348Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Background: Epidemiologic studies evaluating associations between sex steroid hormones and colorectal cancer risk have yielded inconsistent results. To elucidate the role of circulating levels of testosterone, and sex hormone-binding globulin (SHBG) in colorectal cancer risk, we conducted observational and Mendelian randomization (MR) analyses.

Methods: The observational analyses included 333,530 participants enrolled in the UK Biobank with testosterone and SHBG measured. HRs and 95% confidence intervals (CI) were estimated using multivariable Cox proportional hazards models. For MR analyses, genetic variants robustly associated with hormone levels were identified and their association with colorectal cancer (42,866 cases/42,752 controls) was examined using two-sample MR.

Results: In the observational analysis, there was little evidence that circulating levels of total testosterone were associated with colorectal cancer risk; the MR analyses showed a greater risk for women (OR per 1-SD = 1.09; 95% CI, 1.01-1.17), although pleiotropy may have biased this result. Higher SHBG concentrations were associated with greater colorectal cancer risk for women (HR per 1-SD = 1.16; 95% CI, 1.05-1.29), but was unsupported by the MR analysis. There was little evidence of associations between free testosterone and colorectal cancer in observational andMRanalyses.

Conclusions: Circulating concentrations of sex hormones are unlikely to be causally associated with colorectal cancer. Additional experimental studies are required to better understand the possible role of androgens in colorectal cancer development.

Ort, förlag, år, upplaga, sidor
AACR Publications , 2021. Vol. 30, nr 7, s. 1336-1348
Nationell ämneskategori
Cancer och onkologi
Identifikatorer
URN: urn:nbn:se:umu:diva-185900DOI: 10.1158/1055-9965.EPI-20-1690ISI: 000675844700008Scopus ID: 2-s2.0-85109097818OAI: oai:DiVA.org:umu-185900DiVA, id: diva2:1579890
Forskningsfinansiär
NIH (National Institute of Health)EU, FP7, Sjunde ramprogrammetTillgänglig från: 2021-07-12 Skapad: 2021-07-12 Senast uppdaterad: 2023-09-05Bibliografiskt granskad

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Harlid, SophiaHarbs, Justin

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