Bisphenol A exposure, interaction with genetic variants and colorectal cancer via mediating oxidative stress biomarkers

Yao Deng; Heng He; Hao Wan; Na Shen; Jiaoyuan Li; Shanshan Zhang; Qiang Zeng; Jiang Chang; Qing Lu; Rong Zhong; Xiaoping Miao

doi:10.1016/j.envpol.2021.117630

Bisphenol A exposure, interaction with genetic variants and colorectal cancer via mediating oxidative stress biomarkers

Environ Pollut. 2021 Oct 15:287:117630. doi: 10.1016/j.envpol.2021.117630. Epub 2021 Jun 23.

Authors

Yao Deng¹, Heng He², Hao Wan², Na Shen³, Jiaoyuan Li³, Shanshan Zhang², Qiang Zeng⁴, Jiang Chang², Qing Lu⁵, Rong Zhong⁶, Xiaoping Miao²

Affiliations

¹ Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Zhuhai Precision Medical Center, Zhuhai People's Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai, China.
² Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
³ Department of Laboratory Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁵ Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁶ Department of Epidemiology and Biostatistics and Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: zhongr@hust.edu.cn.

PMID: 34182385
DOI: 10.1016/j.envpol.2021.117630

Abstract

Bisphenol A (BPA) may induce oxidative stress as well as the toxicity of colon cancer cells. We hypothesized that BPA exposure and interactions with genetic variants might be associated with colorectal cancer (CRC) risk, and the association might be partly mediated by oxidative stress. We measured urinary BPA and three oxidative stress markers [8-iso-prostaglandinF_2α (8-isoPGF_2α), 8-hydroxydeoxyguanosine (8-OHdG) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)] in 275 new CRC cases and 538 healthy controls. A set of 25 genetic variations in 12 candidate DNA repair genes and 5 metabolic enzyme genes were genotyped by Sequenom MassARRAY approach. In multivariable logistic regression, significant positive associations of CRC risk with BPA, 8-OHdG and HNE-MA were observed. Additionally, 8-OHdG, HNE-MA and 8-isoPGF_2α were significantly positively associated with BPA (P < 0.05). The mediation analysis showed BPA-associated HNE-MA significantly mediated 11.81% of the effect of BPA on CRC risk. Moreover, BPA was found to interact with ERCC5 rs17655 and rs2296147 (both P_{multiplicative} < 0.05) to increase CRC risk. In brief, our results suggested BPA was associated with CRC risk and the positive association of BPA with CRC risk might be partly mediated by the oxidative stress HNE-MA. BPA might interact with ERCC5 rs17655 and rs2296147 to increase CRC risk.

Keywords: Colorectal neoplasms; Gene-environment interaction; Genetic variants; Mediation effect; Oxidative stress.

MeSH terms

Benzhydryl Compounds* / toxicity
Biomarkers
Bisphenol A Compounds
Colorectal Neoplasms* / chemically induced
Colorectal Neoplasms* / genetics
Humans
Oxidative Stress
Phenols

Substances

Benzhydryl Compounds
Biomarkers
Phenols
bisphenol A
Bisphenol A Compounds