DNA repair gene XRCC1 polymorphisms, smoking, and bladder cancer risk

Bladder cancer is the sixth most common cancer in the United States. The ma in identified risk factor is cigarette smoking, which is estimated to contr ibute to up to 50% of new cases in men and 20% in women. Besides containing other carcinogens, cigarette smoke is a rich source of reactive oxygen spe cies (ROS) that can induce a variety of DNA damage, some of which is repair ed by the base excision repair (BER) pathway. The XRCC1 gene protein plays an important role in BER by serving as a scaffold for other repair enzymes and by recognizing single-strand DNA breaks. Three polymorphisms that induc e amino acid changes have been found in codon 194 (exon 6), codon 280 (exon 9), and codon 399 (exon 10) of this gene. We tested whether polymorphisms in XRCC1 were associated with bladder cancer risk and whether this associat ion was modified by cigarette smoking. Therefore, we genotyped for the thre e polymorphisms in 235 bladder cancer cases and 213 controls who had been f requency matched to cases on age, sex, and ethnicity. We found no evidence of an association between the codon 280 variant and bladder cancer risk [od ds ratio (OR), 1.2; 95% confidence interval (CI), 0.6-2.6], We found some e vidence of a protective effect for subjects that carried at least one copy of the codon 194 variant allele relative to those homozygous for the common allele (OR, 0.59; 95% CI, 0.3-1.0), The combined analysis with smoking his tory suggested a possible gene-exposure interaction; however, the results w ere not statistically significant. Similarly, for the codon 399 polymorphis m, our data suggested a protective effect of the homozygous variant genotyp e relative to carriers of either one or two copies of the common allele (OR , 0.70; 95% CI, 0.4-1.3), and provided limited evidence, albeit not statist ically significant, for a gene-smoking interaction.