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

¹ Department of Internal Medicine, ² Cancer Research Institute, and ³ Department of Preventive Medicine, Kyungpook National University; ⁴ Department of Internal Medicine, School of Medicine, Keimyung University; and ⁵ Department of General Surgery, Kyungpook National University Hospital, Daegu, Korea

Requests for reprints: Jae Yong Park, Department of Internal Medicine, Kyungpook National University Hospital, Samduk 2Ga 50, Daegu 700-412, Korea. Phone: 82-53-420-5536; Fax: 82-53-426-2046. E-mail: jaeyong{at}kyungpook.ac.kr

Polymorphisms in the DNA repair genes may be associated with differences in the capacity to repair DNA damage, and so this can influence an individual's 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 P_c (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 P_c = 0.004; and adjusted OR, 0.44; 95% CI, 0.23-0.85; P = 0.014 and P_c = 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)

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