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Fifty single-nucleotide polymorphisms (SNPs) associated with amino acid changes in 36 genes involved in diverse DNA repair pathways were assessed for associations with risk for small cell lung carcinoma (SCLC) by a case–control study consisting of 211 SCLC cases and 685 controls. An SNP, Val83Met, in theMTH1(mutT homolog 1) gene encoding a triphosphatase that hydrolyzes pro-mutagenic oxidized nucleoside triphosphates, such as 8-hydroxy-dGTP and 2-hydroxy-dATP, showed the strongest and a significant association with SCLC risk [odds ratio (OR) = 1.6, 95% confidence interval (CI): 1.2–2.2,P= 0.004], while three other SNPs in theTP53, BLMandSNM1genes, respectively, also showed marginal associations (0.05 &lt;P&lt; 0.1). Another SNP, which causes a nucleotide change in the 5′-UTR ofMTH1transcripts leading to alternative translation initiation, was additionally examined and the SNP also showed a significant association (OR = 1.7, 95% CI: 1.2–2.3,P= 0.002). The two SNPs in theMTH1gene were in linkage disequilibrium, and the OR for carrying a copy of the haplotype consisting of both the risky SNP alleles was 2.0 (95% CI: 1.2–3.2,P= 0.002). The present results indicate that inter-individual differences in MTH1 activities due to SNPs are involved in susceptibility to SCLC.

Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk