Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalase.
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.
Department of Epidemiology, Mailman School of Public Health, Columfbia University, Room-720G, 722 West 168th Street, New York, NY 10032, USA. habidul.ahsan@columbia.edu
Habibul
H
Ahsan
Yu
Y
Chen
Muhammad G
MG
Kibriya
Mohammad N
MN
Islam
Vesna N
VN
Slavkovich
Joseph H
JH
Graziano
Regina M
RM
Santella
D000328:Adult; D020261:Arsenic Poisoning / Q000235:genetics* / Q000652:urine; D001459:Bangladesh; D016022:Case-Control Studies; D002374:Catalase / Q000235:genetics; D004781:Environmental Exposure; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007642:Keratosis / Q000139:chemically induced* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018384:Oxidative Stress / Q000235:genetics*; D009195:Peroxidase / Q000235:genetics; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors
D002374:Catalase; D009195:Peroxidase