Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, Victoria, Australia.
Bristol Medical School, Department of Population Health Sciences, University of Bristol, Bristol, UK.
Br J Sports Med. 2022 Oct;56(20):1157-1170. doi: 10.1136/bjsports-2021-105132. Epub 2022 Sep 6.
Physical inactivity and sedentary behaviour are associated with higher breast cancer risk in observational studies, but ascribing causality is difficult. Mendelian randomisation (MR) assesses causality by simulating randomised trial groups using genotype. We assessed whether lifelong physical activity or sedentary time, assessed using genotype, may be causally associated with breast cancer risk overall, pre/post-menopause, and by case-groups defined by tumour characteristics.
We performed two-sample inverse-variance-weighted MR using individual-level Breast Cancer Association Consortium case-control data from 130 957 European-ancestry women (69 838 invasive cases), and published UK Biobank data (n=91 105-377 234). Genetic instruments were single nucleotide polymorphisms (SNPs) associated in UK Biobank with wrist-worn accelerometer-measured overall physical activity (n=5) or sedentary time (n=6), or accelerometer-measured (n=1) or self-reported (n=5) vigorous physical activity.
Greater genetically-predicted overall activity was associated with lower breast cancer overall risk (OR=0.59; 95% confidence interval (CI) 0.42 to 0.83 per-standard deviation (SD;8 milligravities acceleration)) and for most case-groups. Genetically-predicted vigorous activity was associated with lower risk of pre/perimenopausal breast cancer (OR=0.62; 95% CI 0.45 to 0.87,≥3 vs. 0 self-reported days/week), with consistent estimates for most case-groups. Greater genetically-predicted sedentary time was associated with higher hormone-receptor-negative tumour risk (OR=1.77; 95% CI 1.07 to 2.92 per-SD (7% time spent sedentary)), with elevated estimates for most case-groups. Results were robust to sensitivity analyses examining pleiotropy (including weighted-median-MR, MR-Egger).
Our study provides strong evidence that greater overall physical activity, greater vigorous activity, and lower sedentary time are likely to reduce breast cancer risk. More widespread adoption of active lifestyles may reduce the burden from the most common cancer in women.
观察性研究表明，缺乏身体活动和久坐行为与更高的乳腺癌风险相关，但归因于因果关系较为困难。孟德尔随机化（MR）通过模拟随机试验组使用基因型来评估因果关系。我们评估了终生身体活动或久坐时间，使用基因型评估，是否可能与总体乳腺癌风险、绝经前/后以及通过肿瘤特征定义的病例组相关。
我们使用来自欧洲血统的 130957 名女性（69838 例侵袭性病例）的乳腺癌协会联盟病例对照数据的两样本逆方差加权 MR 以及英国生物库的数据（n=91105-377234）。遗传工具是英国生物库中与腕戴加速度计测量的整体身体活动（n=5）或久坐时间（n=6）相关的单核苷酸多态性（SNP），或加速度计测量（n=1）或自我报告（n=5）的剧烈身体活动。
更高的遗传预测总体活动与整体乳腺癌风险降低相关（OR=0.59；95%置信区间（CI）为 0.42 至 0.83，每标准偏差（SD；8 毫重力加速度）），并且对于大多数病例组也是如此。遗传预测剧烈活动与绝经前/后乳腺癌风险降低相关（OR=0.62；95%CI 0.45 至 0.87，≥3 与 0 自我报告每周天数），对于大多数病例组的估计值也是一致的。更高的遗传预测久坐时间与激素受体阴性肿瘤风险升高相关（OR=1.77；95%CI 1.07 至 2.92/SD（7%时间久坐）），对于大多数病例组的估计值也较高。敏感性分析检查了 pleiotropy（包括加权中位数-MR、MR-Egger），结果仍然稳健。
我们的研究提供了强有力的证据，表明更大的总体身体活动、更大的剧烈活动和更低的久坐时间可能会降低乳腺癌风险。更广泛地采用积极的生活方式可能会减轻女性中最常见癌症的负担。
