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

Pei Ju Liao, Kuang Hung Hsu, Hung Yi Chiou, Chien Jen Chen, Chih Hung Lee

研究成果: 雜誌貢獻文章同行評審

1 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
期刊Biomedical Journal
6
發行號2
DOIs
出版狀態已發佈 - 12月 2021

ASJC Scopus subject areas

  • 醫藥 (全部)

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