Polymorphisms in arsenic metabolism genes, urinary arsenic methylation profile and cancer

Chi Jung Chung, Yu Mei Hsueh, Chyi Huey Bai, Yung Kai Huang, Ya Li Huang, Mo Hsiung Yang, Chien Jen Chen

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

Arsenic-metabolism-related genes can regulate the arsenic methylation process and may influence susceptibility to cancer. We evaluated the roles of arsenic metabolism genes on urinary arsenic profiles of repeated measurement with 15-year follow-up (1988-2004) through general linear model (GLM) and assessed the effect of the changed extent of urinary arsenic profiles on cancer risk. Questionnaire information and blood samples and two urines (1988 and 2004) were collected from 208 subjects in an arseniasis hyperendemic area in Taiwan. Profiles for concentrations of urinary arsenic were determined using HPLC-HG-AAS. The relative proportion of each arsenic species was calculated by dividing the concentration of each arsenic species by the total arsenic concentration. Genotyping was done using the 5 nuclease allelic discrimination (Taqman) assay. The incidence of cancer was identified through linking to the National Cancer Registry Systems. The Cox proportional hazards model and survival curves were used in the analyses. After a 15-year follow-up, baseline monomethylarsonic acid percentage (MMA%) and change in MMA% exhibited a significant dose-response relationship with cancer risk. Individuals with a higher baseline MMA% and a lower change in MMA% had the earliest cancer incidence (statistically significant). Through GLM, significant gene effects of arsenic (+3 oxidation state)-methyltransferase (AS3MT) on MMA%, dimethylarsinic acid percentage (DMA%) and DMA/MMA, purine nucleoside phosphorylase (PNP) on DMA% and glutathione S-transferase omega 2 (GSTO2) on inorganic arsenics (InAs%) were found. Our results show that MMA% might be a potential predictor of cancer risk. The change in MMA% was linked to individual cancer susceptibility related to AS3MT rs3740393.

Original languageEnglish
Pages (from-to)1653-1661
Number of pages9
JournalCancer Causes and Control
Volume20
Issue number9
DOIs
Publication statusPublished - Nov 2009

Keywords

  • Arsenic metabolism
  • AS3MT
  • Cancer
  • GSTO1
  • GSTO2
  • PNP
  • Polymorphism
  • Repeated measurement
  • Urinary arsenic methylation profile

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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