Gene-smoking interactions and gene-histology associations for DNA repair gene polymorphisms (hOGG1 Ser326Cys and XRCC3 Thr241Met) and lung cancer

Genetic susceptibility is thought to be an important modifier of the relationship between smoking and lung cancer. This lung cancer case-only study examined potential gene-environment interactions between smoking and polymorphisms in the DNA repair genes 8-oxoguanine DNA glycosylase (hOGG1) and X-ray repair cross-complementing group 3 (XRCC3), as well as assessed the associations between these polymorphisms and tumour histology.;Compared with the low category, a four-fold interaction with the Thr241Met polymorphism in XRCC3 was found for heavy smokers (95% confidence interval (CI): 1.1--14.9), but no interaction was suggested for the moderate smokers with an OR of 0.94 (95% CI: 0.39--2.25). For the Ser326Cys hOGG1 polymorphism, the ORs were 2.88 (95% CI: 1.21--7.37) and 1.06 (95% CI: 0.33--3.46) for moderate and heavy smokers, respectively.;By histological subtypes, the XRCC3 variant genotypes were over twice as common among patients with squamous cell carcinoma compared with those with adenocarcinoma (Rate Ratio: 2.43, 95% CI: 1.18--5.0) and no difference was found for the hOGG1 polymorphism.;Assuming that smoking behaviour and these polymorphisms are independent in the base population, these results suggest that lung cancer risk associated with smoking may be modified by XRCC3 and, to a lesser extent, hOGGI. Furthermore, this study suggests that XRCC3 plays a more significant role in the etiology of squamous cell carcinoma. Despite the preliminary nature of this study, the strength and biological plausibility of the present findings indicate that these relationships merit further consideration in larger case-control studies. (Abstract shortened by UMI.).