Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK.
Department of Human Genetics, Leiden University Medical Center, 2300 RC Leiden, The Netherlands.
Nutrients. 2022 Dec 9;14(24):5259. doi: 10.3390/nu14245259.
Obesity and upper-body fat distribution are independent, cardiometabolic risk factors but whether they also display comparable associations with cancer risk is unknown. We investigated the causal relationships between body mass index (BMI) and BMI-adjusted waist-to-hip ratio (WHRadjBMI) and cancer risk and searched for potential drivers linking these traits to carcinogenesis using two-sample and multivariable Mendelian randomisation. In women, genetically instrumented higher BMI was associated with lower breast (OR = 0.87, 95% CI 0.81-0.93) and higher endometrial (OR = 1.75, 95% CI 1.55-1.96) cancer risk whilst WHRadjBMI was associated with higher colon cancer risk (OR = 1.22, 95% CI 1.07-1.42). In men, elevated BMI was associated with lower prostate cancer risk (OR = 0.91, 95% CI 0.85-0.98). Mechanistically, testosterone and insulin mediated 21% and 35%, respectively of the total, genetically determined association of BMI with endometrial cancer risk whilst HDL cholesterol and IGF-1 mediated 40% and 22%, respectively of the association between BMI and breast cancer risk. In men, testosterone mediated 21% of the association between BMI and prostate cancer risk. Colon cancer aside, the total amount of body fat might be more important than its location in modulating cancer susceptibility due to differential effects of obesity and fat distribution on adiposity-associated cancer drivers.
肥胖和上半身脂肪分布是独立的代谢性心血管危险因素，但它们是否与癌症风险也存在类似的关联尚不清楚。我们通过两样本和多变量孟德尔随机化研究了体质指数（BMI）和 BMI 调整的腰围臀围比（WHRadjBMI）与癌症风险之间的因果关系，并寻找将这些特征与致癌作用联系起来的潜在驱动因素。在女性中，遗传上较高的 BMI 与较低的乳腺癌（OR=0.87，95%CI 0.81-0.93）和较高的子宫内膜癌（OR=1.75，95%CI 1.55-1.96）风险相关，而 WHRadjBMI 与较高的结肠癌风险相关（OR=1.22，95%CI 1.07-1.42）。在男性中，较高的 BMI 与较低的前列腺癌风险相关（OR=0.91，95%CI 0.85-0.98）。从机制上讲，睾酮和胰岛素分别介导了 BMI 与子宫内膜癌风险之间总遗传相关性的 21%和 35%，而高密度脂蛋白胆固醇和 IGF-1 分别介导了 BMI 与乳腺癌风险之间总遗传相关性的 40%和 22%。在男性中，睾酮介导了 BMI 与前列腺癌风险之间的 21%的相关性。除结肠癌外，由于肥胖和脂肪分布对肥胖相关癌症驱动因素的影响不同，身体脂肪的总量可能比其位置更重要，从而调节癌症易感性。
Zotero 插件