Lung cancer risk and polymorphisms in UGT1A6.

1555 Background: Uridine diphosphoglucuronosyltransferases (UGTs) 1A6, is the only UGT1A isoform expressed in lung tissue. It is responsible for the detoxifying lung carcinogens such as benezo[a]pyrene and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) from cigarette smoking. Methods: The allelic distributions of common UGT1A6 polymorphisms were determined in Chinese, Malay and Indian populations. Polymorphisms with frequencies > 1% were evaluated in a testing set of 72 Chinese cases and 62 Chinese controls, and a validating set of 95 Chinese cases and 100 Chinese controls using pyrosequencing. Results: Significant variations in allelic distribution were observed amongst 3 ethnic groups. SNPs 19T > G, 541A > G and 552A > C were significantly associated with increased lung cancer risk and SNPs 105C > T and IVS1+130G > T were associated with reduced lung cancer risk, in both testing and validating sets. Haplotype analysis suggested strong linkage between 541A>G and 552A > C. The risk of lung cancer highest in subjects with both 19T > G and 552A > C (OR = 16.6, 95% CI 5.9-46.6), and lowest in subjects with both 105C > T and IVS1+130G > T (OR = 0.03, 95% CI 0.002-0.54). Conclusions: Our data suggested that UGT1A6 polymorphisms modulate lung cancer risk and may be used to identify at risk individual for lung cancer screening. No significant financial relationships to disclose.