Polymorphisms of MLH1 and MSH2 genes and the risk of lung cancer among never smokers

Yen Li Lo, Chin Fu Hsiao, Yuh Shan Jou, Gee Chen Chang, Ying Huang Tsai, Wu Chou Su, Kuan Yu Chen, Yuh Min Chen, Ming Shyan Huang, Wan Shan Hsieh, Chien Jen Chen, Chao A. Hsiung

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Abstract

Mismatch repair (MMR) plays an important role in repairing nucleotide mismatches during DNA replication. Defects in MMR genes are associated with some sporadic tumors. MLH1 and MSH2 are two of the MMR genes. We conducted a case-control study to investigate the associations between the risk of lung cancer and genetic polymorphisms in the MLH1 and MSH2 genes. The SNP genotypes were determined in 730 lung cancer patients and 730 healthy controls that were frequency matched for the age, gender, and smoking status. Among the SNP polymorphisms, -93A>G (rs1800734), which is located in the promoter region of MLH1, was significantly associated with the risk of lung cancer. The GG genotype for MLH1 -93A>G was associated with a significantly increased risk of lung cancer compared with the AA genotype among the never-smoking group (adjusted OR. = 1.64, 95% CI. = 1.10-2.44; P = 0.013). Consistently, the haplotype of MLH1 with one -93G risk allele was associated with the risk of lung cancer compared with the AA haplotype among the never-smoking group. Furthermore, the risk of MLH1 -93A>G polymorphism in the never-smoking group related to lung adenocarcinoma was modulated by environmental tobacco smoke (ETS) exposure status, with a significant gene-ETS interaction (P = 0.042). No evidence was found of the association between MSH2 and the lung cancer risk. In conclusion, our data suggest that the MLH1 -93A>G polymorphism may contribute to the etiology of lung cancer, particularly in never smokers. This study also suggests that MLH1 -93A>G polymorphisms and ETS exposure have a role in the tumorigenesis of lung adenocarcinoma among never smokers.

Original languageEnglish
Pages (from-to)280-286
Number of pages7
JournalLung Cancer
Volume72
Issue number3
DOIs
Publication statusPublished - 2011 Jun 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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    Lo, Y. L., Hsiao, C. F., Jou, Y. S., Chang, G. C., Tsai, Y. H., Su, W. C., Chen, K. Y., Chen, Y. M., Huang, M. S., Hsieh, W. S., Chen, C. J., & Hsiung, C. A. (2011). Polymorphisms of MLH1 and MSH2 genes and the risk of lung cancer among never smokers. Lung Cancer, 72(3), 280-286. https://doi.org/10.1016/j.lungcan.2010.10.009