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

Takashi Kohno, Tokuki Sakiyama, Hideo Kunitoh, Koichi Goto, Yutaka Nishiwaki, Daizo Saito, Hiroshi Hirose, Takashi Eguchi, Noriko Yanagitani, Ryusei Saito, Rumie Sasaki-Matsumura, Sachiyo Mimaki, Kaoru Toyama, Seiichiro Yamamoto, Aya Kuchiba, Tomotaka Sobue, Tsutomu Ohta, Misao Ohki, Jun Yokota

研究成果: Article査読

26 被引用数 (Scopus)


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 the MTH1 (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 the TP53, BLM and SNM1 genes, respectively, also showed marginal associations (0.05 < P < 0.1). Another SNP, which causes a nucleotide change in the 5′-UTR of MTH1 transcripts 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 the MTH1 gene 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.

出版ステータスPublished - 2006 12月

ASJC Scopus subject areas

  • 癌研究


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