Cancer Causes & Control

, Volume 20, Issue 9, pp 1653–1661

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
Original paper

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 

References

  1. 1.
    Chen CJ, Chen CW, Wu MM, Kuo TL (1992) Cancer potential in liver, lung, bladder and kidney due to ingested inorganic arsenic in drinking water. Br J Cancer 66:888–892PubMedGoogle Scholar
  2. 2.
    Chen CL, Hsu LI, Chiou HY et al (2004) Ingested arsenic, cigarette smoking, and lung cancer risk: a follow-up study in arseniasis-endemic areas in Taiwan. JAMA 292:2984–2990CrossRefPubMedGoogle Scholar
  3. 3.
    Chiou HY, Hsueh YM, Liaw KF et al (1995) Incidence of internal cancers and ingested inorganic arsenic: a seven-year follow-up study in Taiwan. Cancer Res 55:1296–1300PubMedGoogle Scholar
  4. 4.
    Hsueh YM, Chiou HY, Huang YL et al (1997) Serum beta-carotene level, arsenic methylation capability, and incidence of skin cancer. Cancer Epidemiol Biomarkers Prev 6:589–596PubMedGoogle Scholar
  5. 5.
    Huang YK, Huang YL, Hsueh YM et al (2008) Arsenic exposure, urinary arsenic speciation, and the incidence of urothelial carcinoma: a twelve-year follow-up study. Cancer Causes Control 19:829–839CrossRefPubMedGoogle Scholar
  6. 6.
    Lin S, Shi Q, Nix FB et al (2002) A novel S-adenosyl-L-methionine: arsenic (III) methyltransferase from rat liver cytosol. J Biol Chem 277:10795–10803CrossRefPubMedGoogle Scholar
  7. 7.
    Thomas DJ, Li J, Waters SB et al (2007) Arsenic (+3 oxidation state) methyltransferase and the methylation of arsenicals. Exp Biol Med (Maywood) 232:3–13Google Scholar
  8. 8.
    Drobna Z, Waters SB, Devesa V, Harmon AW, Thomas DJ, Styblo M (2005) Metabolism and toxicity of arsenic in human urothelial cells expressing rat arsenic (+3 oxidation state)-methyltransferase. Toxicol Appl Pharmacol 207:147–159CrossRefPubMedGoogle Scholar
  9. 9.
    Drobna Z, Waters SB, Walton FS, LeCluyse EL, Thomas DJ, Styblo M (2004) Interindividual variation in the metabolism of arsenic in cultured primary human hepatocytes. Toxicol Appl Pharmacol 201:166–177CrossRefPubMedGoogle Scholar
  10. 10.
    Drobna Z, Xing W, Thomas DJ, Styblo M (2006) shRNA silencing of AS3MT expression minimizes arsenic methylation capacity of HepG2 cells. Chem Res Toxicol 19:894–898CrossRefPubMedGoogle Scholar
  11. 11.
    Wood TC, Salavagionne OE, Mukherjee B et al (2006) Human arsenic methyltransferase (AS3MT) pharmacogenetics: gene resequencing and functional genomics studies. J Biol Chem 281:7364–7373CrossRefPubMedGoogle Scholar
  12. 12.
    Mukherjee B, Salavaggione OE, Pelleymounter LL et al (2006) Glutathione S-transferase omega 1 and omega 2 pharmacogenomics. Drug Metab Dispos 34:1237–1246CrossRefPubMedGoogle Scholar
  13. 13.
    Yu L, Kalla K, Guthrie E, Vidrine A, Klimecki WT (2003) Genetic variation in genes associated with arsenic metabolism: glutathione S-transferase omega 1–1 and purine nucleoside phosphorylase polymorphisms in European and indigenous Americans. Environ Health Perspect 111:1421–1427PubMedGoogle Scholar
  14. 14.
    Chowdhury UK, Zakharyan RA, Hernandez A, Avram MD, Kopplin MJ, Aposhian HV (2006) Glutathione-S-transferase-omega [MMA(V) reductase] knockout mice: Enzyme and arsenic species concentrations in tissues after arsenate administration. Toxicol Appl Pharmacol 216:446–457CrossRefPubMedGoogle Scholar
  15. 15.
    Hernandez A, Xamena N, Surralles J et al (2008) Role of the Met(287)Thr polymorphism in the AS3MT gene on the metabolic arsenic profile. Mutat Res 637:80–92PubMedGoogle Scholar
  16. 16.
    Schlawicke EK, Nermell B, Concha G, Stromberg U, Vahter M, Broberg K (2008) Arsenic metabolism is influenced by polymorphisms in genes involved in one-carbon metabolism and reduction reactions. Mutat Res (Article in Press)Google Scholar
  17. 17.
    Engstrom KS, Broberg K, Concha G, Nermell B, Warholm M, Vahter M (2007) Genetic polymorphisms influencing arsenic metabolism: evidence from Argentina. Environ Health Perspect 115:599–605Google Scholar
  18. 18.
    Meza M, Gandolfi AJ, Klimecki WT (2007) Developmental and genetic modulation of arsenic biotransformation: a gene by environment interaction? Toxicol Appl Pharmacol 222:381–387CrossRefPubMedGoogle Scholar
  19. 19.
    Fujihara J, Kunito T, Agusa T et al (2007) Population differences in the human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene polymorphism detected by using genotyping method. Toxicol Appl Pharmacol 225:251–254CrossRefPubMedGoogle Scholar
  20. 20.
    Fujihara J, Soejima M, Koda Y, Agusa T, Kunito T, Takeshita H (2008) Asian specific low mutation frequencies of the M287T polymorphism in the human arsenic (+3 oxidation state) methyltransferase (AS3MT) gene. Mutat Res 654:158–161PubMedGoogle Scholar
  21. 21.
    Tapio S, Grosche B (2006) Arsenic in the aetiology of cancer. Mutat Res -Rev Mutat Res 612:215–246Google Scholar
  22. 22.
    Chen CJ, Hsueh YM, Lai MS et al (1995) Increased prevalence of hypertension and long-term arsenic exposure. Hypertension 25:53–60PubMedGoogle Scholar
  23. 23.
    Hsueh YM, Huang YL, Huang CC et al (1998) Urinary levels of inorganic and organic arsenic metabolites among residents in an arseniasis-hyperendemic area in Taiwan. J Toxicol Environ Health 54:431–444CrossRefGoogle Scholar
  24. 24.
    Chen YC, Amarasiriwardena CJ, Hsueh YM, Christiani DC (2002) Stability of arsenic species and insoluble arsenic in human urine. Cancer Epidemiol Biomarkers Prev 11:1427–1433PubMedGoogle Scholar
  25. 25.
    Steinmaus C, Bates MN, Yuan Y et al (2006) Arsenic methylation and bladder cancer risk in case–control studies in Argentina and the United States. J Occup Environ Med 48:478–488CrossRefPubMedGoogle Scholar
  26. 26.
    Yu RC, Hsu KH, Chen CJ, Froines JR (2000) Arsenic methylation capacity and skin cancer. Cancer Epidemiol Biomarkers Prev 9:1259–1262PubMedGoogle Scholar
  27. 27.
    Radabaugh TR, Sampayo-Reyes A, Zakharyan RA, Aposhian HV (2002) Arsenate reductase II. Purine nucleoside phosphorylase in the presence of dihydrolipoic acid is a route for reduction of arsenate to arsenite in mammalian systems. Chem Res Toxicol 15:692–698CrossRefPubMedGoogle Scholar
  28. 28.
    De CS, Ghosh P, Sarma N et al (2008) Genetic variants associated with arsenic susceptibility: study of purine nucleoside phosphorylase, arsenic (+3) methyltransferase, and glutathione s-transferase omega genes. Environ Health Perspect 116:501–505Google Scholar
  29. 29.
    Marahatta SB, Punyarit P, Bhudisawasdi V, Paupairoj A, Wongkham S, Petmitr S (2006) Polymorphism of glutathione S-transferase omega gene and risk of cancer. Cancer Lett 236:276–281CrossRefPubMedGoogle Scholar
  30. 30.
    Whitbread AK, Tetlow N, Eyre HJ, Sutherland GR, Board PG (2003) Characterization of the human Omega class glutathione transferase genes and associated polymorphisms. Pharmacogenetics 13:131–144CrossRefPubMedGoogle Scholar
  31. 31.
    Arning L, Jagiello P, Wieczorek S, Saft C, Andrich J, Epplen JT (2004) Glutathione S-Transferase Omega 1 variation does not influence age at onset of Huntington’s disease. BMC Med Genet 5:7–10CrossRefPubMedGoogle Scholar
  32. 32.
    Morari EC, Lima AB, Bufalo NE, Leite JL, Granja F, Ward LS (2006) Role of glutathione-S-transferase and codon 72 of P53 genotypes in epithelial ovarian cancer patients. J Cancer Res Clin Oncol 132:521–528CrossRefPubMedGoogle Scholar
  33. 33.
    Ahsan H, Chen Y, Kibriya MG et al (2007) Arsenic metabolism, genetic susceptibility, and risk of premalignant skin lesions in Bangladesh. Cancer Epidemiol Biomarkers Prev 16:1270–1278CrossRefPubMedGoogle Scholar
  34. 34.
    Lindberg AL, Kumar R, Goessler W et al (2007) Metabolism of low-dose inorganic arsenic in a central European population: influence of sex and genetic polymorphisms. Environ Health Perspect 115:1081–1086PubMedCrossRefGoogle Scholar
  35. 35.
    Leite JL, Morari EC, Granja F, Campos GM, Guilhen AC, Ward LS (2007) Influence of the glutathione s-transferase gene polymorphisms on the susceptibility to basal cell skin carcinoma. Rev Med Chil 135:301–306PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2009

Authors and Affiliations

  • Chi-Jung Chung
    • 1
  • Yu-Mei Hsueh
    • 2
  • Chyi-Huey Bai
    • 3
  • Yung-Kai Huang
    • 2
  • Ya-Li Huang
    • 2
  • Mo-Hsiung Yang
    • 4
  • Chien-Jen Chen
    • 5
  1. 1.Graduate Institute of Public HealthTaipei Medical UniversityTaipeiTaiwan
  2. 2.Department of Public Health, School of MedicineTaipei Medical UniversityTaipeiTaiwan
  3. 3.Section of NeurologyShin Kong Wo Ho-Su Memorial HospitalTaipeiTaiwan
  4. 4.Department of Nuclear ScienceNational Tsing-Hua UniversityHsinchuTaiwan
  5. 5.Genomics Research CenterAcademia SinicaTaipeiTaiwan

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