文章：

肥胖相关特征是否通过血清睾酮影响前列腺癌风险？一项孟德尔随机化研究

Do Obesity-Related Traits Affect Prostate Cancer Risk through Serum Testosterone? A Mendelian Randomization Study

原文发布日期：8 October 2023

DOI: 10.3390/cancers15194884

类型: Article

开放获取: 是

英文摘要：

Objective: This study aimed to investigate whether testosterone mediates or confounds the effect of obesity-related traits on prostate cancer (PCa) using Mendelian randomization (MR) analysis. Materials and Methods: Data of obesity-related traits (body mass index [BMI], waist-to-hip ratio [WHR], and waist-to-hip ratio adjusted for body mass index [WHRadjBMI]) were obtained from up to 806,834 people of European ancestry; data of testosterone (bioavailable testosterone [BT], total testosterone [TT], and sex hormone-binding globulin [SHBG]) were extracted from up to 194,453 participants in the UK Biobank; and the summary-level data of PCa (79,194 cases and 61,112 controls) were obtained from the PRACTICAL consortium. Result: The results supported the causal relationship between higher BMI and a reduced risk of PCa (OR = 0.91, 95% confidence interval [CI]: 0.86–0.96). Furthermore, increased BT levels were associated with an elevated risk of PCa (OR = 1.15, 95% CI: 1.06–1.24). Importantly, our analysis revealed a unidirectional causal effect—higher BMI was linked to lower BT levels (beta = −0.27, 95% CI: −0.3–−0.24), but not the other way around. This suggests that BT may mediate the effect of BMI on PCa rather than confound it. Our multivariable MR results further demonstrated that considering BT as a mediator led to the weakening of BMI’s effect on PCa risk (OR = 0.97, 95% CI: 0.90–1.05), while the impact of BT on PCa remained unchanged when accounting for BMI. Moreover, we identified a significant indirect effect of BMI on PCa risk (OR = 0.96, 95% CI: 0.94–0.98). Conclusion: Our study provided genetic evidence that serum BT can mediate the effect of BMI on the risk of PCa, indicating the possible mechanism by which obesity reduces PCa risk.

摘要翻译： 

目的：本研究旨在通过孟德尔随机化分析，探讨睾酮是否介导或混淆了肥胖相关特征对前列腺癌的影响。材料与方法：肥胖相关特征数据（包括体重指数、腰臀比及经体重指数校正的腰臀比）来源于多达806,834名欧洲血统人群；睾酮数据（包括生物可利用睾酮、总睾酮及性激素结合球蛋白）提取自英国生物样本库中多达194,453名参与者；前列腺癌的汇总数据（79,194例病例和61,112例对照）则来自PRACTICAL联盟。结果：研究结果支持较高体重指数与降低前列腺癌风险存在因果关系。此外，生物可利用睾酮水平升高与前列腺癌风险增加相关。重要的是，我们的分析揭示了单向因果效应——较高体重指数与较低生物可利用睾酮水平相关，但反之则不成立。这表明生物可利用睾酮可能介导而非混淆体重指数对前列腺癌的影响。多变量孟德尔随机化结果进一步显示，将生物可利用睾酮作为中介变量时，体重指数对前列腺癌风险的影响减弱，而控制体重指数后生物可利用睾酮对前列腺癌的影响保持不变。此外，我们发现了体重指数对前列腺癌风险的显著间接效应。结论：本研究提供了遗传学证据，表明血清生物可利用睾酮可介导体重指数对前列腺癌风险的影响，这提示了肥胖降低前列腺癌风险的可能机制。

原文链接：

Do Obesity-Related Traits Affect Prostate Cancer Risk through Serum Testosterone? A Mendelian Randomization Study