Polymorphisms in cancer-related pathway genes and lung cancer

We evaluated the associations between potentially functional variants in a comprehensive list of cancer-related genes and lung cancer in a Korean population. A total of 1969 potentially functional single nucleotide polymorphisms (SNPs) of 1151 genes involved in carcinogenesis were evaluated using an Affymetrix custom-made GeneChip in 610 nonsmall cell lung cancer patients and 610 healthy controls. A replication study was conducted in an independent set of 490 cases and 486 controls. 68 SNPs were significantly associated with lung cancer in the discovery set and tested for replication. Among the 68 SNPs, three SNPs (corepressor interacting with RBPJ 1 (CIR1) rs13009079T<C, ribonucleotide reductase M1 (RRM1) rs1465952T<C and solute carrier family 38, member 4 (SLC38A4) rs2429467C<T) consistantly showed significant associations with lung cancer in the replication study. In combined analysis, adjusted odds ratio for CIR1 rs13009079T<C, RRM1 rs1465952T<C and SLC38A4 rs2429467C<T were 0.69, 0.71 and 0.73, respectively (p=4×10^-5, 0.01 and 0.001, respectively) under the dominant model. The relative mRNA expression level of CIR1 was significantly associated with rs13009079T<C genotypes in normal lung tissues (p_trend=0.03). These results suggest that the three SNPs, particularly CIR1 rs13009079T<C, may play a role in the pathogenesis of lung cancer.