We found that no significant
effect was apparent between OGG1 Ser326Cys and lung FDA approved Drug Library concentration cancer risk, in combination to smoking status. BMS345541 It has been reported that the OGG1 Cys allele in Japanese patients is associated with an increased risk for lung cancer [8, 9]. The variant OGG1 is deficient in its catalytic activity, was not stimulated by the AP endonuclease . A recent report has suggested that OGG1 Ser326Cys is not associated with lung cancer by meta-analysis . Therefore, our finding in a Japanese population is consistent with the results from the meta-analysis study. On the other hand, we found that the MUTYH His/His genotype was significantly associated with increased risk of lung cancer. Previous study has shown that the identified variants of the MUTYH gene, containing Gln324His, were unlikely to predispose significantly to the risk for lung cancer in Caucasians . SU5402 The discrepancy between this study and ours might reflect the differences in genetic background,
carcinogen exposure in different populations or sample sizes. Recent study has reported that the MUTYH enzyme activity in Gln324His polymorphism was only 66% active from the substrates compared with the wild type . It was reported that the 2-OH-A level compared to repair of adenine opposite 8-oxo-G was increased in human cancerous tissues compared to normal tissues . Therefore, it is also possible that the MUTYH enzyme having 324His variation may have partially a reduced activity in repair of 2-OH-A opposite guanine. This suggested that MUTYH Gln324His might also be associated with risk for lung cancer, related to the decreased MUTYH enzyme activity. In different histological types of lung cancer, MUTYH His/His genotype Astemizole was a significantly borderline association for both adenocarcinoma and squamous cell carcinoma, that suggested a potential interaction between this polymorphism and lung cancer risk regardless these subtypes. Moreover, the result of the joint effect between tobacco
smoking and MUTYH His/His genotype for the risk of lung cancer was a significant increase in smokers, whereas that was not in non-smokers. If the sample size had been larger, the result in non-smokers might have been significant. This finding suggested that the effect of MUTYH Gln324His for lung cancer risk is not different between smoking habits. In conclusion, these results suggest that the MUTYH Gln324His polymorphism appear to play an important role in modifying the risk for lung cancer in the Japanese population. To the best of our knowledge, our study is the first case-control study to evaluate the association between the MUTYH Gln324His and lung cancer risk in Japanese.