Department of Epidemiology, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine and China International Cooperation Center for Environment and Human Health, Nanjing Medical University, Nanjing, Jiangsu, P.R. China.
Cancer Epidemiol Biomarkers Prev. 2021 Jul;30(7):1302-1304. doi: 10.1158/1055-9965.EPI-21-0472.
Sex hormones have been suggested as a contributor to gender disparity in incidence and mortality of colorectal cancer, but previous observational studies on endogenous sex hormones and colorectal cancer risk have led to contradictory results. Leveraging the large-scale UK biobank resource, Dimou and colleagues performed both observational and Mendelian randomization (MR) analyses to investigate the association of serum testosterone and sex hormone binding globulin concentrations with the risk of colorectal cancer. Although the findings provide little evidence for independent roles of the hormones in colorectal cancer, further interrogation of possible mediating effects of sex hormones on the causal pathways of colorectal cancer could deepen our understanding of colorectal cancer etiology and improve tailored prevention. While MR analysis is useful for inferring causality in observational studies, the current null results should be interpreted with caution because of insufficient statistical power and predefined assumptions of linearity. Moreover, given the widespread use of testosterone supplementation in older men to restore age-related decline of endogenous concentrations, large and long-term randomized controlled trials are required to clarify the effect of testosterone on colorectal cancer risk, which would provide critical evidence for health decision making..
性激素被认为是导致结直肠癌发病率和死亡率性别差异的一个因素，但之前关于内源性性激素与结直肠癌风险的观察性研究得出了相互矛盾的结果。Dimou 及其同事利用英国生物库的大规模资源，进行了观察性和孟德尔随机化 (MR) 分析，以研究血清睾丸酮和性激素结合球蛋白浓度与结直肠癌风险之间的关系。尽管这些发现几乎没有提供证据表明这些激素在结直肠癌中具有独立作用，但进一步探究性激素对结直肠癌因果途径的可能中介作用，可以加深我们对结直肠癌病因学的理解，并改善针对性预防。虽然 MR 分析可用于推断观察性研究中的因果关系，但由于统计效力不足和线性的预设假设，目前的阴性结果应谨慎解释。此外，鉴于在老年男性中广泛使用睾丸酮补充剂来恢复内源性浓度的年龄相关性下降，需要进行大型和长期的随机对照试验来阐明睾丸酮对结直肠癌风险的影响，这将为健康决策提供关键证据。
