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

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Abstract

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.

Original languageEnglish
Pages (from-to)2448-2454
Number of pages7
JournalCarcinogenesis
Volume27
Issue number12
DOIs
Publication statusPublished - 2006 Dec

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Small Cell Lung Carcinoma
Single Nucleotide Polymorphism
Genes
Odds Ratio
Confidence Intervals
5' Untranslated Regions
Linkage Disequilibrium
Nucleosides
Individuality
DNA Repair
Haplotypes
Case-Control Studies
Nucleotides
Alleles
Amino Acids

ASJC Scopus subject areas

  • Cancer Research

Cite this

Kohno, T., Sakiyama, T., Kunitoh, H., Goto, K., Nishiwaki, Y., Saito, D., ... Yokota, J. (2006). Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk. Carcinogenesis, 27(12), 2448-2454. https://doi.org/10.1093/carcin/bgl095

Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk. / Kohno, Takashi; Sakiyama, Tokuki; Kunitoh, Hideo; Goto, Koichi; Nishiwaki, Yutaka; Saito, Daizo; Hirose, Hiroshi; Eguchi, Takashi; Yanagitani, Noriko; Saito, Ryusei; Sasaki-Matsumura, Rumie; Mimaki, Sachiyo; Toyama, Kaoru; Yamamoto, Seiichiro; Kuchiba, Aya; Sobue, Tomotaka; Ohta, Tsutomu; Ohki, Misao; Yokota, Jun.

In: Carcinogenesis, Vol. 27, No. 12, 12.2006, p. 2448-2454.

Research output: Contribution to journalArticle

Kohno, T, Sakiyama, T, Kunitoh, H, Goto, K, Nishiwaki, Y, Saito, D, Hirose, H, Eguchi, T, Yanagitani, N, Saito, R, Sasaki-Matsumura, R, Mimaki, S, Toyama, K, Yamamoto, S, Kuchiba, A, Sobue, T, Ohta, T, Ohki, M & Yokota, J 2006, 'Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk', Carcinogenesis, vol. 27, no. 12, pp. 2448-2454. https://doi.org/10.1093/carcin/bgl095
Kohno T, Sakiyama T, Kunitoh H, Goto K, Nishiwaki Y, Saito D et al. Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk. Carcinogenesis. 2006 Dec;27(12):2448-2454. https://doi.org/10.1093/carcin/bgl095
Kohno, Takashi ; Sakiyama, Tokuki ; Kunitoh, Hideo ; Goto, Koichi ; Nishiwaki, Yutaka ; Saito, Daizo ; Hirose, Hiroshi ; Eguchi, Takashi ; Yanagitani, Noriko ; Saito, Ryusei ; Sasaki-Matsumura, Rumie ; Mimaki, Sachiyo ; Toyama, Kaoru ; Yamamoto, Seiichiro ; Kuchiba, Aya ; Sobue, Tomotaka ; Ohta, Tsutomu ; Ohki, Misao ; Yokota, Jun. / Association of polymorphisms in the MTH1 gene with small cell lung carcinoma risk. In: Carcinogenesis. 2006 ; Vol. 27, No. 12. pp. 2448-2454.
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abstract = "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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AU - Kohno, Takashi

AU - Sakiyama, Tokuki

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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

PY - 2006/12

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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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