Single Nucleotide Polymorphisms in Myeloperoxidase and Catalase Genes Increase Susceptibility for Arsenic-Induced Hyperkeratosis

Habibul Ahsan, MD, Regina M. Santella, Ph.D. and Joseph H. Graziano, Ph.D.
Columbia University Health Science
P42ES10349 and P30ES09089

Background: Chronic exposure to arsenic, usually through contaminated drinking water, is known to cause skin and other cancers in humans. This is unfortunately readily apparent in areas of the world where arsenic exposure is high such as Bangladesh and parts of South America. Continuing on previous research in Bangladesh by this team of investigators, this report focuses on whether single nucleotide polymorphisms in two oxidative stress genes are associated with increased risk of arsenic-induced hyperkeratotic skin lesions (precursors of skin cancer) in a case-control study also carried out in Bangladesh.

Advance: Carriers of the susceptible myeloperoxidase and catalase genotypes were at about twice the risk for hyperkeratosis. When combined with high arsenic exposure, carriers of the susceptible myeloperoxidase gene had six times the risk of hyperkeratosis than did subjects with low arsenic exposure and the low-risk genotype. Similarly, high arsenic exposure and high-risk catalase genotype was associated with about a four-fold risk of hyperkeratosis than low exposure and low-risk genotype.

Implication: These studies, although based on small numbers of subjects, suggest that the oxidative stress genes myeloperoxidase and catalase may influence the risk of arsenic-induced premalignant hyperkeratotic skin lesions. This group is currently conducting a larger epidemiologic prospective cohort study. Findings from this study, if confirmed in the larger study, may have important research and policy implications. Recent estimates suggest that the life-time burden of internal cancers due to arsenic exposure in Bangladesh is expected to be at least doubled. Currently, no specific chemoprevention strategies for preventing arsenic induced cancers are known. Since a vast number of people have already accumulated years of chronic exposure, the study findings may guide researchers in designing and testing specific biomedical/public health interventions by incorporating knowledge of inherent variations in susceptibility to arsenic effects. From the general policy perspective, the findings should reinforce the importance of reducing arsenic exposure in the population.

Citation: Ahsan H, Chen Y, Kibriya MG, Islam MN, Slavkovich VN, Graziano JH, Santella RM. Susceptibility to arsenic-induced hyperkeratosis and oxidative stress genes myeloperoxidase and catalase. Cancer Lett. 2003 Nov 10;201(1):57-65.