Genetic polymorphisms in XRCC1 genes and colorectal cancer susceptibility

The objective of this study is to investigate the association among the polymorphisms of XRCC1 gene, smoking, drinking, family history of tumors, and the risk of colorectal cancer (CRC) in the population of Han nationality in Jiangsu Province, China.

A case-control study of 320 patients with CRC and 350 cancer-free subjects as a control group was conducted. The three polymorphic sites, codons 194, 280, and 399, of XRCC1 genes were analyzed by PCR-RFLP.

We find that heavy smoking (>500 cigarettes per year) significantly increased the susceptibility of CRC (OR=1.89, 95% confidence interval (CI) 1.27-2.84) after stratification by total smoking amount. There was also significant difference between cases and controls when family history of tumors (OR=2.96, 95% CI 1.76-4.99) was considered. Comparing with individuals carrying XRCC1 399Arg/Arg genotype, the subjects with 399Arg/Gln (OR=1.46, 95% CI 1.06-2.01) or 399Gln/Gln genotype (OR=1.93, 95% CI 1.05-3.54) had a significantly increased risk for CRC. Taking smoking and drinking habits into consideration, we found that subjects with heavy smoking history and XRCC1 194Arg allele had the significantly increased risk for CRC (OR=2.91, 95% CI 1.35-6.24). Individuals, who carry 399Gln allele and have a heavy smoking (OR=2.72, 95% CI 1.52-4.89) or drinking habit (OR=1.98, 95% CI 1.06-3.67), also have higher risk. In smoking population, 194Arg (P=0.491) and 399Gln (P=0.912) had not significantly increased risk for CRC, so did 399Gln (P=0.812) in smoking population.

Individuals carrying XRCC1 399Gln allele with a smoking or drinking habit were in increased risk, and heavy-smoking subjects with 194Arg allele also have higher risk for CRC in the Han nationality population of Jiangsu Province, which also showed a positive correlation with exposure dose of tobacco. But XRCC1 399Gln allele or 194Arg allele were not independent risk factors for CRC in smoking or drinking population.