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.
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.
Environ Pollut. 2021 Oct 15;287:117630. doi: 10.1016/j.envpol.2021.117630. Epub 2021 Jun 23.
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 (8-isoPGF), 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 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 < 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.
双酚 A（BPA）可能会引起氧化应激以及结肠癌细胞的毒性。我们假设 BPA 暴露以及与遗传变异的相互作用可能与结直肠癌（CRC）风险相关，并且这种关联可能部分通过氧化应激来介导。我们测量了 275 例新 CRC 病例和 538 例健康对照者的尿 BPA 和三种氧化应激标志物[8-异前列腺素 F（8-isoPGF）、8-羟基脱氧鸟苷（8-OHdG）和 4-羟基-2-壬烯醛-巯基尿酸（HNE-MA）]。通过 Sequenom MassARRAY 方法对 12 个候选 DNA 修复基因和 5 个代谢酶基因中的 25 个遗传变异进行了基因分型。在多变量逻辑回归中，观察到 CRC 风险与 BPA、8-OHdG 和 HNE-MA 呈显著正相关。此外，8-OHdG、HNE-MA 和 8-isoPGF 与 BPA 呈显著正相关（P<0.05）。中介分析显示，BPA 相关的 HNE-MA 显著介导了 BPA 对 CRC 风险的 11.81%的作用。此外，发现 BPA 与 ERCC5 rs17655 和 rs2296147 相互作用（均 P<0.05），从而增加 CRC 风险。总之，我们的研究结果表明，BPA 与 CRC 风险相关，BPA 与 CRC 风险的正相关可能部分通过 HNE-MA 介导的氧化应激来介导。BPA 可能与 ERCC5 rs17655 和 rs2296147 相互作用，从而增加 CRC 风险。
