Carcinogenesis Advance Access published online on June 14, 2006
Carcinogenesis, doi:10.1093/carcin/bgl095
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1 Center for Medical Genomics, National Cancer Center Research Institute, Tokyo, Japan; Biology Division, National Cancer Center Research Institute, Tokyo, Japan
* To whom correspondence should be addressed. 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. A SNP, Val83Met, in the MTH1 (mutT homologue 1) gene encoding a triphosphatase that hydrolyzes promutagenic 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.
Received March 2, 2006
Revised May 14, 2006
Accepted May 19, 2006
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION
Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk
Takashi Kohno 1,
Tokuki Sakiyama 2,
Hideo Kunitoh 3,
Koichi Goto 4,
Yutaka Nishiwaki 4,
Daizo Saito 5,
Hiroshi Hirose 6,
Takashi Eguchi 7,
Noriko Yanagitani 8,
Ryusei Saito 8,
Rumie Sasaki-Matsumura 9,
Sachiyo Mimaki 2,
Kaoru Toyama 9,
Seiichiro Yamamoto 10,
Aya Kuchiba 11,
Tomotaka Sobue 10,
Tsutomu Ohta 2,
Misao Ohki 2,
and
Jun Yokota 1 *
2 Center for Medical Genomics, National Cancer Center Research Institute, Tokyo, Japan
3 Division of Thoracic Oncology, National Cancer Center Hospital, Tokyo, Japan
4 Division of Thoracic Oncology, National Cancer Center Hospital East, Chiba Japan
5 Department of Endoscopy and Gastrointestinal Oncology, National Cancer Center Hospital, Tokyo, Japan
6 Health Center, Keio University School of Medicine, Tokyo, Japan; Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
7 Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan
8 First Department of Internal Medicine, Gunma University School of Medicine, Gunma, Japan
9 Biology Division, National Cancer Center Research Institute, Tokyo, Japan
10 Statistics and Cancer Control Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan
11 Statistics and Cancer Control Division, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan; Department of Biostatistics/Epidemiology and Preventive Health Sciences, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
Jun Yokota, E-mail: jyokota{at}gan2.ncc.go.jp
Abstract
Notes: T. Kohno and T. Sakiyama contributed equally to this work.
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