Methionine synthase and thymidylate synthase gene polymorphisms and colorectal adenoma risk: The self defense forces study

Shinichiro Yoshimitsu, Makiko Morita, Tadamichi Hamachi, Shinji Tabata, Hiroshi Abe, Osamu Tajima, Kousaku Uezono, Ohnaka Keizo, Suminori Kono

Research output: Contribution to journalArticle

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Abstract

Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3′ untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95% confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (≥30mL/d), but not in those with low alcohol consumption (interaction P=0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas.

Original languageEnglish
JournalMolecular Carcinogenesis
Volume51
Issue numberSUPPL. 1
DOIs
Publication statusPublished - Oct 1 2012

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5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
Thymidylate Synthase
Adenoma
Genotype
Genes
Oxidoreductases
Alcohol Drinking
Alleles
Tandem Repeat Sequences
3' Untranslated Regions
Genetic Polymorphisms
Colonoscopy
Polyps
Folic Acid
Genetic Promoter Regions
Carcinogenesis
Carbon
Odds Ratio
Alcohols
Confidence Intervals

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cancer Research

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Methionine synthase and thymidylate synthase gene polymorphisms and colorectal adenoma risk : The self defense forces study. / Yoshimitsu, Shinichiro; Morita, Makiko; Hamachi, Tadamichi; Tabata, Shinji; Abe, Hiroshi; Tajima, Osamu; Uezono, Kousaku; Keizo, Ohnaka; Kono, Suminori.

In: Molecular Carcinogenesis, Vol. 51, No. SUPPL. 1, 01.10.2012.

Research output: Contribution to journalArticle

Yoshimitsu, Shinichiro ; Morita, Makiko ; Hamachi, Tadamichi ; Tabata, Shinji ; Abe, Hiroshi ; Tajima, Osamu ; Uezono, Kousaku ; Keizo, Ohnaka ; Kono, Suminori. / Methionine synthase and thymidylate synthase gene polymorphisms and colorectal adenoma risk : The self defense forces study. In: Molecular Carcinogenesis. 2012 ; Vol. 51, No. SUPPL. 1.
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abstract = "Folate-mediated one-carbon metabolism has been implicated in colorectal carcinogenesis. We investigated associations of functional genetic polymorphisms of methionine synthase (MTR), MTR reductase (MTRR), and thymidylate synthase (TS) with colorectal adenomas. The study subjects were 455 cases of colorectal adenomas and 1052 controls with no polyp at colonoscopy. Genotypes were determined for MTR A2756G, MTRR A66G and two polymorphisms in the TS gene, 28-bp tandem repeat polymorphism in the promoter enhancer region (TSER) and 6-bp deletion polymorphism at position 1494 in the 3′ untranslated region (TS 1494del6). We also examined the alcohol-genotype and gene-gene interactions on adenoma risk. The GG genotype of MTR A2756G was associated with an increased risk of colorectal adenomas; odds ratios for AG and GG versus AA genotype were 0.99 (95{\%} confidence interval 0.78-1.26) and 1.72 (1.04-2.82), respectively. The increase in the risk associated with MTR 2756GG genotype was evident in men with high alcohol consumption (≥30mL/d), but not in those with low alcohol consumption (interaction P=0.03). Men who were homozygous for the TSER double-repeat allele had a slightly decreased risk of colorectal adenomas as compared with those homozygous for the TSER triple-repeat allele. Neither MTRR A66G nor TS 1494del6 was associated with colorectal adenomas. There was no measurable interaction either between MTR A2756G and MTRR A66G or between TSER and TS 1494del6. MTR A2756G appears to be associated with colorectal adenoma risk differently according to alcohol consumption. The MTR-catalyzed reaction may play an important role in the development of colorectal adenomas.",
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