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

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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.

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Acknowledgments

The study was supported by grants from the National Science Council of the ROC (NSC 86-2314-B-038-038, NSC 87-2314-B-038-029, NSC-88-2314-B-038-112, NSC-89-2314-B038-049, SC-89-2320-B038-013, NSC-90-2320-B-038-021, NSC91-3112-B-038-0019, NSC92-3112-B-038-001, NSC93-3112-B-038-001, NSC94-2314-B-038-023, NSC-95-2314-B-038-007, NSC- 96-2314-B038-003 and NSC 97-2314-B-038-015-MY3).

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Authors and Affiliations

  1. Graduate Institute of Public Health, Taipei Medical University, Taipei, Taiwan

    Chi-Jung Chung

  2. Department of Public Health, School of Medicine, Taipei Medical University, No. 250 Wu-Hsing Street, Taipei, 110, Taiwan

    Yu-Mei Hsueh, Yung-Kai Huang & Ya-Li Huang

  3. Section of Neurology, Shin Kong Wo Ho-Su Memorial Hospital, Taipei, Taiwan

    Chyi-Huey Bai

  4. Department of Nuclear Science, National Tsing-Hua University, Hsinchu, Taiwan

    Mo-Hsiung Yang

  5. Genomics Research Center, Academia Sinica, Taipei, Taiwan

    Chien-Jen Chen

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  1. Chi-Jung Chung
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  2. Yu-Mei Hsueh
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Correspondence to Yu-Mei Hsueh.

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Chung, CJ., Hsueh, YM., Bai, CH. et al. Polymorphisms in arsenic metabolism genes, urinary arsenic methylation profile and cancer. Cancer Causes Control 20, 1653–1661 (2009). https://doi.org/10.1007/s10552-009-9413-0

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  • DOI: https://doi.org/10.1007/s10552-009-9413-0

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