TY - JOUR
T1 - Circulating levels of testosterone, sex hormone binding globulin and colorectal cancer risk
T2 - Observational and mendelian randomization analyses
AU - Dimou, Niki
AU - Mori, Nagisa
AU - Harlid, Sophia
AU - Harbs, Justin
AU - Martin, Richard M.
AU - Smith-Byrne, Karl
AU - Papadimitriou, Nikos
AU - Timothy Bishop, D.
AU - Casey, Graham
AU - Colorado-Yohar, Sandra M.
AU - Cotterchio, Michelle
AU - Cross, Amanda J.
AU - Le Marchand, Loic
AU - Lin, Yi
AU - Offit, Kenneth
AU - Charlotte Onland-Moret, N.
AU - Peters, Ulrike
AU - Potter, John D.
AU - Rohan, Thomas E.
AU - Weiderpass, Elisabete
AU - Gunter, Marc J.
AU - Murphy, Neil
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research Inc.. All rights reserved.
PY - 2021/7
Y1 - 2021/7
N2 - 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.
AB - 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.
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U2 - 10.1158/1055-9965.EPI-20-1690
DO - 10.1158/1055-9965.EPI-20-1690
M3 - Article
C2 - 33879453
AN - SCOPUS:85109097818
SN - 1055-9965
VL - 30
SP - 1336
EP - 1348
JO - Cancer Epidemiology Biomarkers and Prevention
JF - Cancer Epidemiology Biomarkers and Prevention
IS - 7
ER -