遗传预测的身体活动水平与较低的结直肠癌风险相关：一项孟德尔随机化研究。

Genetically predicted physical activity levels are associated with lower colorectal cancer risk: a Mendelian randomisation study.

机构信息

Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, UK.

Cancer Research UK Edinburgh Centre, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.

出版信息

Br J Cancer. 2021 Mar;124(7):1330-1338. doi: 10.1038/s41416-020-01236-2. Epub 2021 Jan 29.

DOI:10.1038/s41416-020-01236-2

PMID:33510439

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8007642/

Abstract

BACKGROUND

We conducted a Mendelian randomisation (MR) study to investigate whether physical activity (PA) causes a reduction of colorectal cancer risk and to understand the contributions of effects mediated through changes in body fat.

METHODS

Common genetic variants associated with self-reported moderate-to-vigorous PA (MVPA), acceleration vector magnitude PA (AMPA) and sedentary time were used as instrumental variables. To control for confounding effects of obesity, we included instrumental variables for body mass index (BMI), body fat percentage, waist circumference and arm, trunk and leg fat ratios. We analysed the effect of these instrumental variables in a colorectal cancer genome-wide association study comprising 31,197 cases and 61,770 controls of European ancestry by applying two-sample and multivariable MR study designs.

RESULTS

We found decreased colorectal cancer risk for genetically represented measures of MVPA and AMPA that were additional to effects mediated through genetic measures of obesity. Odds ratio and 95% confidence interval (CI) per standard deviation increase in MVPA and AMPA was 0.56 (0.31, 1.01) and 0.60 (0.41, 0.88), respectively. No association has been found between sedentary time and colorectal cancer risk. The proportion of effect mediated through BMI was 2% (95% CI: 0, 14) and 32% (95% CI: 12, 46) for MVPA and AMPA, respectively.

CONCLUSION

These findings provide strong evidence to reinforce public health measures on preventing colorectal cancer that promote PA at a population level regardless of body fatness.

摘要

背景

我们进行了一项孟德尔随机化（MR）研究，旨在探讨体力活动（PA）是否会降低结直肠癌风险，并了解通过体脂变化介导的作用的贡献。

方法

使用与自我报告的中等到剧烈体力活动（MVPA）、加速度矢量幅度 PA（AMPA）和久坐时间相关的常见遗传变异作为工具变量。为了控制肥胖的混杂影响，我们纳入了身体质量指数（BMI）、体脂百分比、腰围和手臂、躯干和腿部脂肪比例的工具变量。我们通过应用两样本和多变量 MR 研究设计，在一项欧洲血统的结直肠癌全基因组关联研究中分析了这些工具变量对 31197 例病例和 61770 例对照的影响。

结果

我们发现，MVPA 和 AMPA 的遗传代表性措施与通过肥胖遗传措施介导的作用相结合，可以降低结直肠癌的风险。MVPA 和 AMPA 每标准偏差增加的优势比和 95%置信区间（CI）分别为 0.56（0.31，1.01）和 0.60（0.41，0.88）。没有发现久坐时间与结直肠癌风险之间的关联。通过 BMI 介导的作用比例分别为 MVPA 和 AMPA 的 2%（95%CI：0，14）和 32%（95%CI：12，46）。