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DNA Methylation in RARβ Gene as a Mediator of the Association Between Healthy Lifestyle and Breast Cancer: A Case–Control Study

Authors Wang X, Liu Y, Sun H, Ge A, Li D, Fu J, Li Y, Pang D, Zhao Y

Received 3 January 2020

Accepted for publication 20 May 2020

Published 18 June 2020 Volume 2020:12 Pages 4677—4684

DOI https://doi.org/10.2147/CMAR.S244606

Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 2

Editor who approved publication: Dr Xueqiong Zhu


Xuan Wang, 1 Yupeng Liu, 1 Hongru Sun, 1 Anqi Ge, 1 Dapeng Li, 1 Jinming Fu, 1 Yan Li, 1 Da Pang, 2 Yashuang Zhao 1

1Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin 150081, Heilong Jiang Province, People’s Republic of China; 2Department of Breast Surgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin 150081, Heilong Jiang Province, People’s Republic of China

Correspondence: Yashuang Zhao
Department of Epidemiology, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150081, People’s Republic of China
Tel/ Fax +86-0451-87502823
Email Zhao_yashuang@263.net
Da Pang
Department of Breast Surgery, The Affiliated Cancer Hospital of Harbin Medical University, Harbin, Heilongjiang Province 150081, People’s Republic of China
Tel/ Fax +86-0451-86298330
Email pangda@ems.hrbmu.edu.cn

Purpose: Lifestyle factors and methylation in the retinoic acid receptor β (RARβ) gene are associated with breast cancer (BC). This study aims to examine the mediation effect of RARβ methylation on the association between healthy lifestyle and BC in Chinese women.
Patients and Methods: This case–control study consisted of 408 BC patients and 573 controls. A healthy lifestyle score (HLS) was constructed based on diet, alcohol use, physical activity, body mass index and smoking. The mediation effect of RARβ methylation in peripheral blood leukocytes was assessed in a causal mediation model using R package Lavaan.
Results: A higher HLS was significantly associated with lower risk of BC (P-value< 0.001). In mediation analyses, the total effect of HLS on BC measured as a regression coefficient was significant (− 0.237). The indirect effects of HLS on RARβ methylation (− 0.153) and RARβ methylation on BC (0.220) were both significant. The significant mediation effect of RARβ methylation on the HLS-BC association was estimated at 14.3%.
Conclusion: The relationship between healthy lifestyle and BC is partly mediated by RARβ methylation, suggesting that epigenetic modifications play a role in the underlying mechanisms in response to lifestyles and contribute to the development of BC.

Keywords: healthy lifestyle score, retinoic acid receptor β, mediation effect, population study

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