基因组标记物和与无机砷代谢相关的尿甲基化能力对砷污染地区居民癌症发生的联合作用：平均随访 15 年的队列子样本。
Joint effects of genomic markers and urinary methylation capacity associated with inorganic arsenic metabolism on the occurrence of cancers among residents in arseniasis-endemic areas: A cohort subset with average fifteen-year follow-up.
机构信息
Department of Health Care Administration, Oriental Institute of Technology, New Taipei City, Taiwan.
Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan; Laboratory for Epidemiology, Department of Health Care Management, Chang Gung University, Taoyuan, Taiwan; Department of Emergency Medicine, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Department of Urology, Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan; Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Taoyuan, Taiwan; Department of Safety, Health and Environmental Engineering, Ming Chi University of Technology, New Taipei City, Taiwan.
出版信息
Biomed J. 2021 Dec;44(6 Suppl 2):S218-S225. doi: 10.1016/j.bj.2020.10.005. Epub 2020 Oct 13.
BACKGROUND
Chronic exposure to inorganic arsenic results in many cancers in susceptible persons. The metabolism of inorganic arsenic and genomic susceptibility are thought to be associated with cancer occurrence.
METHODS
This study aims to examine the interaction of genomic susceptibility markers and urinary methylation capacity indicators involved in inorganic arsenic metabolism with all-cancer occurrence. This study conducted a follow-up on 96 residents to determine their urinary inorganic arsenic metabolites and genomic assay from an arseniasis area. Among them, 24 cancer developed. Multivariable Cox proportional hazards model was used to determine and estimate the candidate independent variables for cancer development.
RESULTS
The residents with high inorganic arsenic exposure, high primary methylation index (PMI; MMA/InAs) (but lower secondary methylation index (SMI)), and non-heterogeneity type of genomic markers, including GSTO1, AS3MT, and MPO, tend to develop cancers. Subjects with higher PMI are at higher risk of developing cancers (HR = 1.66; 95% CI = 1.30-2.12). Cancer occurrence was greater among the CC type of GSTO1 (HR = 3.33; 95% CI = 1.11-10.00), CC type of AS3MT (HR = 19.21; 95% CI = 1.16-318.80), and AA type of MPO (HR = 13.40; 95% CI = 1.26-142.40). After adjusting confounders, a mutually moderating effect was revealed between genomic markers and methylation capacity on cancer occurrence.
CONCLUSIONS
This study found the hypermethylation responses to inorganic arsenic exposure and an array of genomic markers may increase the susceptibility of a wide range of organ cancers. The findings indicated a high-risk arsenic-exposed population to develop cancers. The phenotype of arsenic metabolism and genomic polymorphism suggested a potential preventive strategy for arsenic carcinogenesis.
背景
无机砷的慢性暴露会导致易感人群患上多种癌症。人们认为无机砷的代谢和基因组易感性与癌症的发生有关。
方法
本研究旨在研究无机砷代谢相关的基因组易感性标志物和尿甲基化能力指标与所有癌症发生的相互作用。本研究对来自砷病区的 96 名居民进行了随访，以确定他们的尿无机砷代谢物和基因组检测结果。其中 24 人发生了癌症。采用多变量 Cox 比例风险模型确定并估计癌症发生的候选独立变量。
结果
无机砷暴露水平高、初级甲基化指数（MMA/InAs）较高（但次级甲基化指数（SMI）较低）、基因组标志物（GSTO1、AS3MT 和 MPO）非杂合型的居民更容易患上癌症。具有较高 PMI 的受试者患癌症的风险更高（HR=1.66；95%CI=1.30-2.12）。GSTO1 的 CC 型（HR=3.33；95%CI=1.11-10.00）、AS3MT 的 CC 型（HR=19.21；95%CI=1.16-318.80）和 MPO 的 AA 型（HR=13.40；95%CI=1.26-142.40）癌症发生率更高。调整混杂因素后，发现基因组标志物和甲基化能力之间存在相互调节作用，这会影响癌症的发生。
结论
本研究发现，对无机砷暴露的过度甲基化反应和一系列基因组标志物可能会增加广泛的器官癌症的易感性。研究结果表明，高危砷暴露人群更容易患癌症。砷代谢表型和基因组多态性提示了一种潜在的砷致癌预防策略。
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