Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individual's susceptibility to smoking-related cancer. We investigated the association between the ؊93G3 A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 ؊93G3 A polymorphism was typed in 372 lung cancer patients and 371 healthy controls that were frequency-matched for age and sex. There was no significant association between the hMLH1 ؊93G3 A genotype and the risk for adenocarcinoma or small cell carcinoma. However, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma compared with both the GG genotype (adjusted OR ؍ 2.02; 95% CI ؍ 1.15-3.55; p ؍ 0.014) and the combined GG and GA genotype (adjusted OR ؍ 1.83; 95% CI ؍ 1.24 -2.71; p ؍ 0.003). When the subjects were stratified by smoking exposure, the AA genotype was associated with a significantly increased risk for squamous cell carcinoma in lighter smokers (< 39 pack-years; adjusted OR ؍ 1.95; 95% CI ؍ 1.03-3.66; p ؍ 0.039) compared with the combined GG and GA genotype, whereas there was no significant association in heavier smokers (> 39 pack-years; adjusted OR ؍ 1.47; 95% CI ؍ 0.82-2.61). These results suggest that the hMLH1 ؊93G3 A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung.
Background: Polymorphisms in Epidermal Growth Factor Receptor (EGFR) gene may influence EGFR production and/or activity, thereby modulating susceptibility to lung cancer. To test this hypothesis, we investigated the association between polymorphisms in the EGFR gene and the risk of lung cancer in a Korean population.
p73, a structural and functional homologue of p53, plays an important role in modulating cell-cycle control and apoptosis. MDM2 represses the transcriptional activity of p73 and thus attenuates its activity. Based on the interaction between p73 and MDM2 in cell-cycle control and apoptosis, we investigated the association between p73 G4C14-to-A4T14 and MDM2 309T > G polymorphisms, alone and in combination, on the risk of lung cancer in a Korean population. The p73 and MDM2 genotypes were determined in 582 lung cancer patients and in 582 healthy control subjects who were frequency-matched for age and gender. The p73 AT/AT and MDM2 309 GG genotypes were associated with a nonsignificant increased risk of lung cancer (adjusted odds ratio [OR] = 1.37, 95% confidence interval [CI] = 0.83-2.24; and adjusted OR = 1.29, 95% CI = 0.92-1.80, respectively), compared with their wild-type genotypes, respectively. When the p73 and MDM2 polymorphisms were combined, the risk of lung cancer increased in a dose-dependent manner as the number of variant alleles increased (Ptrend = 0.01). Subjects with three or four variant alleles were at a significantly increased risk of lung cancer (adjusted OR = 1.74, 95% CI = 1.11-2.74, P = 0.02) compared to subjects with zero variant allele. These results suggest an additive effect of the p73 and MDM2 variant alleles on an increased risk of lung cancer.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.