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Lipids, Anthropometric Measures, Smoking and Physical Activity Mediate the Causal Pathway From Education to Breast Cancer in Women: A Mendelian Randomization Study

孟德尔随机化 医学 乳腺癌 肿瘤科 体质指数 优势比 内科学 调解 置信区间 癌症 人口学 妇科 产科 遗传学 基因型 社会学 法学 政治学 基因 生物 遗传变异
作者
Hongkai Li,Lei Hou,Yuanyuan Yu,Xiaoru Sun,Xinhui Liu,Yi-Fan Yu,Sijia Wu,Yina He,Yutong Wu,Limin He,Fuzhong Xue
出处
期刊:Journal of Breast Cancer [Korean Breast Cancer Society]
卷期号:24 (6): 504-504 被引量:1
标识
DOI:10.4048/jbc.2021.24.e53
摘要

We aimed to investigate whether obtaining a higher level of education was causally associated with lower breast cancer risk and to identify the causal mechanism linking them.The main data analysis used publicly available summary-level data from 2 large genome-wide association study consortia. Mendelian randomization (MR) analysis used 65 genetic variants derived from the Social Science Genetic Association Consortium as instrumental variables for years of schooling. The outcomes from the Breast Cancer Association Consortium (BCAC) were the overall breast cancer risk (122,977 cases/105,974 controls in women) and the two subtypes: estrogen receptor (ER)-positive breast cancer and ER-negative breast cancer. Fixed and random effects inverse variance weighted methods were used to estimate the causal effects, along with other additional MR methods for sensitivity analyses.Results showed that each additional standard deviation of 4.2 years of education was causally associated with a 27% lower risk of ER-negative breast cancer (odds ratio, 0.73; 95% confidence interval, 0.64-0.84; p-value < 0.001). This finding was consistent with the results of the sensitivity analyses. Physical activities can help improve the protective effect of education against breast cancer, with relatively large mediation proportions. Education increases the risk of ER-positive breast cancer due to alterations in high-density lipoprotein level, triglyceride level, height, waist-to-hip ratio, body mass index, and smoking status, with relative medium mediation proportions. Other mediators including low-density lipoprotein, hip circumference, number of cigarettes smoked per day, time spent performing light physical activity, and performing vigorous physical activity for > 10 minutes explain a small part of the causal effect of education on the risk of developing breast cancer, and their mediation proportion is approximately 1%.A low level of education is a causal risk factor in the development of breast cancer as it is associated with poor lipid profile, obesity, smoking, and types of physical activity.
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