Ding Lishan, Chen Qingliang, Liang Hao, Shen Meng, Zheng Ming, Li Zhaojun
First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Henan, China.
Department of Radioactive Interventions, Henan No. 3 Provincial People's Hospital, Henan, China.
Arch Med Sci. 2024 Nov 2;20(6):1957-1967. doi: 10.5114/aoms/195271. eCollection 2024.
Previous research suggests a potential association between physical activity (PA) and breast cancer (BC), but the causal relationship remains uncertain. The aim of this study was to explore the causal relationship between PA and BC through Mendelian randomization (MR) analysis.
Genome-wide association studies utilizing data from the UK Biobank baseline were employed to analyze PA phenotypes, encompassing 460,376 participants. Summary data for BC, comprising 122,977 cases and 105,974 controls, were obtained from the BC Association Consortium. The cases were further categorized based on estrogen receptor status into estrogen receptor-positive breast cancer (ER+ BC) and estrogen receptor-negative breast cancer (ER- BC). The inverse variance weighted method was employed as the primary approach for two-sample MR. Additionally, the MR-PRESSO (MR-Pleiotropy RESidual Sum and Outlier) method was utilized to eliminate outliers. Tests for heterogeneity and pleiotropy were conducted to enhance result accuracy. Furthermore, multivariable Mendelian randomization was performed, adjusting for potential confounders to ensure result stability.
MR analysis was employed to assess the causal link between PA and BC. Two-sample MR analysis revealed a genetic prediction indicating that walking for pleasure was associated with decreased risk of ER+ BC (odds ratio (OR) = 0.302, 95% CI = 0.105-0.872, = 0.027), while other physical activities were not significantly correlated with BC, ER+ BC and ER- BC. These findings remained reliable and consistent in the sensitivity analysis, including Cochran's Q and MR-Egger regression. Furthermore, reverse MR analysis suggested that BC did not exert a notable impact on PA.
Our findings suggest that engaging in leisure walking is associated with a reduced risk of ER+ BC. Nevertheless, additional research is warranted to comprehensively elucidate the underlying mechanisms and strengthen the causal relationship.
先前的研究表明身体活动（PA）与乳腺癌（BC）之间可能存在关联，但因果关系仍不确定。本研究的目的是通过孟德尔随机化（MR）分析探讨PA与BC之间的因果关系。
利用英国生物银行基线数据进行全基因组关联研究，以分析PA表型，涉及460376名参与者。从乳腺癌协会联盟获得了包含122977例病例和105974名对照的BC汇总数据。病例根据雌激素受体状态进一步分为雌激素受体阳性乳腺癌（ER + BC）和雌激素受体阴性乳腺癌（ER - BC）。逆方差加权法被用作两样本MR的主要方法。此外，使用MR - PRESSO（MR - 多效性残差和异常值）方法来消除异常值。进行异质性和多效性检验以提高结果准确性。此外，进行了多变量孟德尔随机化，对潜在混杂因素进行调整以确保结果稳定性。
采用MR分析评估PA与BC之间的因果联系。两样本MR分析显示一个遗传预测，即休闲散步与ER + BC风险降低相关（优势比（OR）= 0.302，95％CI = 0.105 - 0.872，P = 0.027），而其他身体活动与BC、ER + BC和ER - BC无显著相关性。这些发现在敏感性分析（包括Cochran's Q和MR - Egger回归）中仍然可靠且一致。此外，反向MR分析表明BC对PA没有显著影响。
我们的研究结果表明，进行休闲散步与降低ER + BC风险相关。然而，需要进一步研究以全面阐明潜在机制并加强因果关系。
