Journal Article
Polymorphisms in XPD (Asp312Asn and Lys751Gln) genes, sunburn and arsenic-related skin lesions
McCarty, KM; Smith, TJ; Zhou, W; Gonzalez, E; Quamruzzaman, Q; Rahman, M; Mahiuddin, G; Ryan, L; Su, L; Christiani, DC
Carcinogenesis
ISSN: 0143-3334
EISSN: 1460-2180
BACKGROUND: Single-nucleotide polymorphisms in genes related to DNA repair capacity and ultraviolet exposure have not been well investigated in relation to skin lesions associated with arsenic exposure. This population based case-control study, of 600 cases and 600 controls, frequency matched on age and gender in Pabna, Bangladesh, in 2001-2002, investigated the association and potential effect modification between polymorphisms in Xeroderma Pigmentosum complementation group D (XPD) (Lys751Gln and Asp312Asn) genes, tendency to sunburn and arsenic-related skin lesions. METHODS: Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULT: No significant association was observed between skin lesions and the XPD 312 Asp/Asn (adjusted OR = 0.87, 95% CI = 0.65-1.15) Asn/Asn (adjusted OR = 0.76, 95% CI = 0.50-1.15) (referent Asp/Asp); XPD 751 Lys/Gln (adjusted OR = 0.92, 95% CI = 0.69-1.23) Gln/Gln (adjusted OR = 0.98, 95% CI = 0.66-1.45) (referent Lys/Lys). While we did not observe any evidence of effect modification of these polymorphisms on the association between well arsenic concentration and skin lesions, we did observe effect modification between these polymorphisms and sunburn tendency and arsenic-related skin lesions. Individuals with the heterozygote or homozygote variant forms (Asp/Asn or Asn/Asn) had half the risk of skin lesions (OR = 0.45, 95% CI = 0.29-0.68) compared with those with the wild-type XPDAsp312Asn genotype (Asp/Asp) and individuals with heterozygote or homozygote variant forms (Lys/Gln or Gln/Gln) had half the risk of skin lesions (OR = 0.47, 95% CI = 0.31-0.72) compared with those with the wild-type XPDLys751Gln genotype (Lys/Lys), within the least sensitive strata of sunburn severity. We observed effect modification on the multiplicative scale for XPD 751 and XPD 312. CONCLUSION: XPD polymorphisms modified the relationship between tendency to sunburn and skin lesions in an arsenic exposed population. Further study is necessary to explore the effect of XPD polymorphisms and sun exposure on risk of arsenic-related skin lesions.
Adult: Amino Acid Substitution/*genetics: Arsenic/*adverse effects/analysis: Asparagine/genetics: Aspartic Acid/genetics: Case-Control Studies: Female: Genetic Predisposition to Disease: Glutamine/genetics: Humans: Lysine/genetics: Male: *Polymorphism, Single Nucleotide: Skin Diseases/chemically induced/*genetics: Sunburn/*genetics: Water Supply/analysis: Xeroderma Pigmentosum Group D Protein/*genetics
