TY - JOUR
T1 - Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk
AU - Kohno, Takashi
AU - Sakiyama, Tokuki
AU - Kunitoh, Hideo
AU - Goto, Koichi
AU - Nishiwaki, Yutaka
AU - Saito, Daizo
AU - Hirose, Hiroshi
AU - Eguchi, Takashi
AU - Yanagitani, Noriko
AU - Saito, Ryusei
AU - Sasaki-Matsumura, Rumie
AU - Mimaki, Sachiyo
AU - Toyama, Kaoru
AU - Yamamoto, Seiichiro
AU - Kuchiba, Aya
AU - Sobue, Tomotaka
AU - Ohta, Tsutomu
AU - Ohki, Misao
AU - Yokota, Jun
N1 - Funding Information:
This work was supported by Grants-in-Aid from the Ministry of Health, Labour and Welfare for Research on Human Genome and Tissue Engineering and for Cancer Research (16S-1), and a Grant-in-Aid from the Program for Promotion of Fundamental Studies in Health Sciences of the Organization for Pharmaceutical Safety. We thank Dr Ikuo Saito, Dr Matsuhiko Hayashi and Dr Keiichi Hirao of the Keio University School of Medicine; Dr Teruhiko Yoshida, Dr Hiromi Sakamoto, Dr Kimio Yoshimura and Dr Shunpei Ohnami of the National Cancer Center Research Institute; and Ms Toyoko Matsumoto and Ms Fumiko Koh of the National Cancer Center Hospital East for their help in collecting blood samples in Keio University. We also thank Dr Kouichi Minato and Dr Shinichi Ishihara of Gunma Prefectural Cancer Center for their collection of blood samples from lung cancer patients. N.Y. was an awardee of a Research Resident Fellowship from the Foundation for Promotion of Cancer Research in Japan during the study. Funding to pay the Open Access publication charges for this article was provided by xxxxx.
PY - 2006/12
Y1 - 2006/12
N2 - 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.
AB - 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.
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U2 - 10.1093/carcin/bgl095
DO - 10.1093/carcin/bgl095
M3 - Article
C2 - 16774934
AN - SCOPUS:33845354863
SN - 0143-3334
VL - 27
SP - 2448
EP - 2454
JO - Carcinogenesis
JF - Carcinogenesis
IS - 12
ER -
