Section of Nutrition and Metabolism, International Agency for Research on Cancer, Lyon, France.
Department of Radiation Sciences, Oncology, Umeå University, Umeå, Sweden.
Cancer Epidemiol Biomarkers Prev. 2021 Jul;30(7):1336-1348. doi: 10.1158/1055-9965.EPI-20-1690. Epub 2021 Apr 20.
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.
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.
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 and MR analyses.
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.
Our results from large-scale analyses provide little evidence for sex hormone pathways playing a causal role in colorectal cancer development..
评估性激素与结直肠癌风险之间关联的流行病学研究结果不一致。为了阐明循环睾酮和性激素结合球蛋白（SHBG）水平在结直肠癌风险中的作用，我们进行了观察性和孟德尔随机化（MR）分析。
观察性分析包括英国生物库中 333530 名参与者，测量了他们的睾酮和 SHBG 水平。使用多变量 Cox 比例风险模型估计 HR 和 95%置信区间（CI）。对于 MR 分析，鉴定出与激素水平密切相关的遗传变异，并使用两样本 MR 分析它们与结直肠癌（42866 例/42752 例对照）的关联。
在观察性分析中，几乎没有证据表明循环总睾酮水平与结直肠癌风险相关；MR 分析显示，女性风险更高（每 1-SD 的 OR=1.09；95%CI，1.01-1.17），尽管可能存在偏倚。较高的 SHBG 浓度与女性结直肠癌风险增加相关（每 1-SD 的 HR=1.16；95%CI，1.05-1.29），但 MR 分析不支持这一结果。在观察性和 MR 分析中，游离睾酮与结直肠癌之间几乎没有关联。
循环性激素浓度不太可能与结直肠癌有因果关系。需要进一步的实验研究来更好地理解雄激素在结直肠癌发展中的可能作用。
我们的大规模分析结果几乎没有证据表明性激素途径在结直肠癌的发展中起因果作用。
