Abstract
BackgroundX-ray cross-complementing group 1 (XRCC1) polymorphisms affect DNA repair capacity and may therefore be of importance in colorectal carcinogenesis. Alcohol consumption, an important risk factor for colorectal cancer, may induce carcinogenesis through DNA damage caused by the toxic effects of alcohol or its metabolites. Therefore, we examined the associations of XRCC1 Arg399Gln, Arg280His, and Arg194Trp polymorphisms with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk.MethodsThis case-control study in Fukuoka, Japan including 685 cases and 778 controls. The cases were incident patients with histologically confirmed colorectal adenocarcinoma. The controls were randomly selected community subjects.ResultsThe XRCC1 399Gln/Gln genotype was significantly associated with colorectal cancer risk (adjusted odds ratio [OR] 1.57, 95% CI 1.01–2.42; relative to 399Arg/Arg genotype). The association was strongest in individuals with high alcohol consumption. The Arg280His polymorphism modified the association between alcohol consumption and colorectal cancer risk (interaction P = 0.049). The OR of colorectal cancer in individuals with the 280His allele was 0.45 (95% CI 0.26–0.78) as compared with the 280Arg/Arg genotype limited to the 399Gln allele (interaction P = 0.001). The adjusted ORs for 399Gln/Gln-280Arg/Arg-194Arg/Arg and 399Arg/Gln-280Arg/Arg-194Arg/Trp were 1.71 (95% CI 1.02–2.87) and 1.57 (95% CI 1.05–2.33), respectively, with 399Arg/Arg-280Arg/Arg-194Arg/Arg as reference (interaction P = 0.418).ConclusionsThe findings are additional evidence that individuals with the XRCC1 399Gln/Gln genotype have an increased risk of colorectal cancer, and that XRCC1 polymorphisms have an important role in colorectal cancer risk associated with alcohol consumption or gene-gene interaction.
Highlights
Colorectal cancer is one of the most common cancers in North America and Western Europe,[1,2] and its incidence has been increasing in Japan.[2]
We examined the associations of these 3 genetic polymorphisms of the X-ray cross-complementing group 1 (XRCC1) gene with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk in Japan
The crude and adjusted odds ratios (ORs) of colorectal cancer for the 399Gln/Gln genotype as compared with the 399Arg/Arg genotype were significantly higher than unity (Table 2)
Summary
Colorectal cancer is one of the most common cancers in North America and Western Europe,[1,2] and its incidence has been increasing in Japan.[2]. For the XRCC1 399Gln allele, 2 previous studies showed an increased risk of colorectal cancer,[9,10] while other case-control studies showed no positive association with the that allele,[11,12,13,14,15,16,17] including a small study in Japan.[13] Discrepant findings have been reported for the XRCC1 Arg194Trp and Arg280His polymorphisms. Alcohol intake is associated with the production of reactive oxygen species—including oxygen radicals, lipid peroxidation, and acetaldehyde—which cause DNA damage that can be repaired by the DNA base-excision repair pathway.[22] polymorphisms of the base-excision repair gene (XRCC1) may be a risk factor for colorectal cancer and modify the association between alcohol consumption and colorectal cancer risk. We examined the associations of these 3 genetic polymorphisms of the XRCC1 gene with colorectal cancer and the impact of the association between alcohol consumption and colorectal cancer risk in Japan
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