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

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

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)57-65
Number of pages9
JournalCancer Letters
Volume201
Issue number1
DOIs
StatePublished - Nov 10 2003

Keywords

  • Arsenic
  • CAT
  • Gene-environmental interaction
  • Genetic susceptibility
  • MPO
  • Oxidative stress genes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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