Role of polymorphisms in codons 143 and 160 of the O⁶-alkylguanine DNA alkyltransferase gene in lung cancer risk

O⁶-Alkylguanine DNA alkyltransferase (AGT) plays an important role in the repair of alkylating agent-induced DNA damage and protection from the carcinogenic effects of environmental agents. To examine the importance of the AGT codon 143 and codon 160 polymorphisms in risk for lung cancer and to assess the prevalence of these polymorphisms in different racial groups, we performed genotype analysis of lung cancer patients and matched controls. The prevalence of the AGT(143Val) allele in controls was 0.07 in Caucasians and 0.03 in African Americans. The AGT(143Val) allele was not detected in an unmatched Asian control cohort. The prevalence of the AGT(160Arg) variant allele was 0.01 in Caucasians, 0.02 in African Americans, and 0.03 in Asians. A marginally significant association was observed between the AGT codon 143 (isoleucine/valine) genotype and risk for lung cancer (odds ratio = 2.1; 95% confidence interval = 1,01-4.7). The prevalence of the AGT(160Arg) variant allele was similar in lung cancer cases versus matched controls. These results suggest that the AGT codon 143 polymorphism may play an important role in risk for lung cancer.