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Division of Clinical Sciences, National Cancer Institute, NIH, Bethesda, Maryland 20892 [D. R., J. A. T., P. R. T.]; Yunnan Tin Corporation, Gejiu, Yunnan Province, People’s Republic of China [S-X. Y.]; New Chemical Entities, Inc., Thetagen Division, Bothell, Washington 98011 [M. R. A.]; Cancer Institute, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China [Y-L. Q.]; Information Management Services, Inc., Silver Spring, Maryland 20904 [M. J. B., C. A. G.]; Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland 21205 [Y. E.]; H. Lee Moffit Cancer Center and Research Institute, Tampa, Florida 33612 [M. S. T.]
We explored the association between polymorphisms of the DNA repair gene XRCC1 (codons 194, 280, and 399) and lung cancer risk in a case-control study nested within a cohort of tin miners. Cases were those diagnosed with lung cancer over 6 years of follow-up (n = 108). Two controls, matched on age and sex, were selected for each case by incidence density sampling. Of the three polymorphisms, only the XRCC1 Arg280His allele was associated with increased lung cancer risk (odds ratio, 1.8; 95% confidence interval, 1.0–3.4) after adjustment for radon and tobacco exposure. In addition, individuals with the variant Arg280His allele who were alcohol drinkers seemed to be at higher risk for lung cancer compared with those with the homozygous wild-type genotype. Conversely, individuals with the variant Arg194Trp allele who were alcohol drinkers seemed to be at lower risk for lung cancer compared with those with the homozygous wild-type genotype. Polymorphisms of XRCC1 appear to influence risk of lung cancer and may modify risk attributable to environmental exposures.
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