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

Hongkai Li; Lei Hou; Yuanyuan Yu; Xiaoru Sun; Xinhui Liu; Yifan Yu; Sijia Wu; Yina He; Yutong Wu; Li He; Fuzhong Xue

doi:10.4048/jbc.2021.24.e53

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저자정보: Hongkai Li (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Lei Hou (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Yuanyuan Yu (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medici) Xiaoru Sun (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Xinhui Liu (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Yifan Yu (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Sijia Wu (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Yina He (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Yutong Wu (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Li He (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin) Fuzhong Xue (Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.24 No.6

발행연도: 2021.12

수록면: 504 - 519 (16page)

DOI: 10.4048/jbc.2021.24.e53

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Purpose: 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. Methods: 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: 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%. Conclusion: 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.

#Breast Neoplasms #Education #Mediation Analysis #Mendelian Randomization Analysis #Meta-Analysis

참고문헌 (33)

참고문헌 신청

Harbeck N / 2017 / Breast cancer / Lancet 389:1134~1150

Global Burden of Disease Cancer Collaboration / 2017 / Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: a systematic analysis for the global burden of disease study / JAMA Oncol 3:524~548

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Hongkai Li

소속기관 Department of Epidemiology and Health Statistics School of Public Health Cheeloo College of Medicin