Kyung Mee Kim

-93G→A polymorphism of hMLH1 and risk of primary lung cancer

Polymorphisms in DNA repair genes may be associated with differences in the repair capacity of DNA damage and may thereby influence an individuals susceptibility to smoking‐related cancer. We investigated the association between the −93G→A polymorphism in the hMLH1 gene and the risk of lung cancer in a Korean population. The hMLH1 −93G→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 −93G→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 −93G→A polymorphism could be used as a marker of genetic susceptibility to squamous cell carcinoma of the lung.

Polymorphisms in the hMSH2 Gene and the Risk of Primary Lung Cancer

Polymorphisms in the DNA repair genes may be associated with differences in the capacity to repair DNA damage, and so this can influence an individuals susceptibility to lung cancer. To test this hypothesis, we investigated the association of hMSH2 −118T>C, IVS1+9G>C, IVS10+12A>G, and IVS12−6T>C genotypes and their haplotypes with the risk of lung cancer in a Korean population. The hMSH2 genotypes were determined in 432 lung cancer patients and in 432 healthy controls who were frequency matched for age and gender. The hMSH2 haplotypes were estimated based on a Bayesian algorithm using the Phase program. The presence of at least one IVS10+12G allele was associated with a significantly decreased risk of adenocarcinoma, as compared with the IVS10+12AA genotype [adjusted odds ratio (OR), 0.59; 95% confidence interval (95% CI), 0.40-0.88; P = 0.01], and the presence of at least one IVS12-6C allele was associated with a significantly increased risk of adenocarcinoma, as compared with the IVS12-6TT genotype (adjusted OR, 1.52; 95% CI, 1.02-2.27; P = 0.04). Consistent with the results of the genotyping analysis, the TGGT haplotype with no risk allele was associated with a significantly decreased risk of adenocarcinoma, as compared with the TCAC haplotype with two risk allele [i.e., IVS10+12A and IVS12-6C allele; adjusted OR, 0.49; 95% CI, 0.30-0.78; P = 0.003 and Pc (Bonferroni corrected P value) = 0.012]. The effect of the hMSH2 haplotypes on the risk of adenocarcinoma was statistically significant in the never smokers and younger individuals (adjusted OR, 0.45; 95% CI, 0.27-0.75; P = 0.002 and Pc = 0.004; and adjusted OR, 0.44; 95% CI, 0.23-0.85; P = 0.014 and Pc = 0.028, respectively) but not in the ever-smokers and older individuals. These results suggest that the hMSH2 polymorphisms and their haplotypes may be an important genetic determinant of adenocarcinoma of the lung, particularly in never smokers. (Cancer Epidemiol Biomarkers Prev 2006;15(4):762–8)