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Title: Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalase.

Authors: Ahsan, Habibul; Chen, Yu; Kibriya, Muhammad G; Islam, Mohammad N; Slavkovich, Vesna N; Graziano, Joseph H; Santella, Regina M

Published In Cancer Lett, (2003 Nov 10)

Abstract: Chronic exposure to inorganic arsenic is known to cause non-melanocytic skin and internal cancers in humans. We examined whether genetic susceptibility, as determined by single nucleotide polymorphisms -463G-->A and -262C-->T in the oxidative stress genes myeloperoxidase (MPO) and catalase (CAT), respectively, are associated with the risk of arsenic-induced hyperkeratotic skin lesions-precursors of skin cancer-in a case-control study in Bangladesh. Carriers of the susceptible MPO and CAT genotypes were at elevated risk (OR 2.1 and 95% CI 0.7-6.2 for MPO; OR 1.9 and 95% CI 0.8-4.7 for CAT) of hyperkeratosis after adjustment for arsenic exposure and other covariates. Subjects carrying the high-risk MPO genotype and with high arsenic exposure were at almost six times (OR 5.8; 95% CI 1.1-30.1) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Similarly, highly exposed subjects carrying the high-risk CAT genotype were at more than four times (OR 4.6; 95% CI 1.4-15.6) elevated risk of developing hyperkeratosis as compared to those carrying the low-risk genotype and with low arsenic exposure. Our findings, although based on small numbers, suggest that the oxidative stress genes MPO and CAT may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions.

PubMed ID: 14580687 Exiting the NIEHS site

MeSH Terms: Adult; Arsenic Poisoning/genetics*; Arsenic Poisoning/urine; Bangladesh; Case-Control Studies; Catalase/genetics; Environmental Exposure; Female; Genetic Predisposition to Disease*; Genotype; Humans; Keratosis/chemically induced*; Keratosis/genetics*; Male; Middle Aged; Oxidative Stress/genetics*; Peroxidase/genetics; Polymerase Chain Reaction; Polymorphism, Single Nucleotide/genetics; Risk Factors

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