Original paper

Cancer Causes & Control

, Volume 20, Issue 9, pp 1653-1661

First online:

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

  • Chi-Jung ChungAffiliated withGraduate Institute of Public Health, Taipei Medical University
  • , Yu-Mei HsuehAffiliated withDepartment of Public Health, School of Medicine, Taipei Medical University Email author 
  • , Chyi-Huey BaiAffiliated withSection of Neurology, Shin Kong Wo Ho-Su Memorial Hospital
  • , Yung-Kai HuangAffiliated withDepartment of Public Health, School of Medicine, Taipei Medical University
  • , Ya-Li HuangAffiliated withDepartment of Public Health, School of Medicine, Taipei Medical University
  • , Mo-Hsiung YangAffiliated withDepartment of Nuclear Science, National Tsing-Hua University
  • , Chien-Jen ChenAffiliated withGenomics Research Center, Academia Sinica

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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.

Keywords

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