title: A distinct and replicable variant of the squamous cell carcinoma gene inositol polyphosphate-5-phosphatase modifies the susceptibility of arsenic-associated skin lesions in Bangladesh.
abstract: BACKGROUND
  Single-nucleotide polymorphisms (SNPs) in inflammation, one-carbon metabolism, and skin cancer genes might influence susceptibility to arsenic-induced skin lesions.
  
  
  METHODS
  A case-control study was conducted in Pabna, Bangladesh (2001-2003), and the drinking-water arsenic concentration was measured for each participant. A panel of 25 candidate SNPs was analyzed in 540 cases and 400 controls. Logistic regression was used to estimate the association between each SNP and the potential for gene-environment interactions in the skin lesion risk, with adjustments for relevant covariates. Replication testing was conducted in an independent Bangladesh population with 488 cases and 2,794 controls.
  
  
  RESULTS
  In the discovery population, genetic variants in the one-carbon metabolism genes phosphatidylethanolamine N-methyltransferase (rs2278952, P for interaction  = .004; rs897453, P for interaction = .05) and dihydrofolate reductase (rs1650697, P for interaction = .02), the inflammation gene interleukin 10 (rs3024496, P for interaction =.04), and the skin cancer genes inositol polyphosphate-5-phosphatase (INPP5A; rs1133400, P for interaction = .03) and xeroderma pigmentosum complementation group C (rs2228000, P for interaction = .01) significantly modified the association between arsenic and skin lesions after adjustments for multiple comparisons. The significant gene-environment interaction between a SNP in the INPP5A gene (rs1133400) and water arsenic with respect to the skin lesion risk was successfully replicated in an independent population (P for interaction = .03).
  
  
  CONCLUSIONS
  Minor allele carriers of the skin cancer gene INPP5A modified the odds of arsenic-induced skin lesions in both main and replicative populations. Genetic variation in INPP5A appears to have a role in susceptibility to arsenic toxicity.
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Wei Jie
authors.initials: WJ
authors.lastname: Seow
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Wen-Chi
authors.initials: WC
authors.lastname: Pan
authors.affiliation: College of Public Health and Human Sciences, Oregon State University, Corvallis, Oregon.
authors.forename: Molly L
authors.initials: ML
authors.lastname: Kile
authors.affiliation: Department of Health Studies, University of Chicago, Chicago, Illinois.
authors.forename: Lin
authors.initials: L
authors.lastname: Tong
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Andrea A
authors.initials: AA
authors.lastname: Baccarelli
authors.affiliation: Dhaka Community Hospital, Dhaka, Bangladesh.
authors.forename: Quazi
authors.initials: Q
authors.lastname: Quamruzzaman
authors.affiliation: Dhaka Community Hospital, Dhaka, Bangladesh.
authors.forename: Mahmuder
authors.initials: M
authors.lastname: Rahman
authors.affiliation: Dhaka Community Hospital, Dhaka, Bangladesh.
authors.forename: Golam
authors.initials: G
authors.lastname: Mostofa
authors.affiliation: UChicago Research Bangladesh, Dhaka, Bangladesh.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Rakibuz-Zaman
authors.affiliation: Department of Health Studies, University of Chicago, Chicago, Illinois.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Kibriya
authors.affiliation: Department of Health Studies, University of Chicago, Chicago, Illinois.
authors.forename: Habibul
authors.initials: H
authors.lastname: Ahsan
authors.affiliation: Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: Xihong
authors.initials: X
authors.lastname: Lin
authors.affiliation: Department of Environmental Health, Harvard School of Public Health, Boston, Massachusetts.
authors.forename: David C
authors.initials: DC
authors.lastname: Christiani
mesh_terms: D000328:Adult; D020261:Arsenic Poisoning / Q000201:enzymology / Q000235:genetics*; D001459:Bangladesh; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D000072181:Inositol Polyphosphate 5-Phosphatases; D008297:Male; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012878:Skin Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*
chemical_list: D010744:Phosphoric Monoester Hydrolases; C000606429:INPP5A protein, human; D000072181:Inositol Polyphosphate 5-Phosphatases
keywords: arsenic; environmental health; genetic polymorphisms; skin cancer; susceptibility