Genetic polymorphisms of the glycine N-methyltransferase and prostate cancer risk in the health professionals follow-up study

Marcelo Chen, Yi Ling Huang, Yu Chuen Huang, Irene M. Shui, Edward Giovannucci, Yen Ching Chen, Yi Ming Arthur Chen

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Purpose: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). Methods: A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. Results: The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95% confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥16GAs/≥16GAs genotype was associated with decreased risk of prostate cancer when compared with the <16GAs/<16GAs genotype (odds ratio (OR) = 0.68; 95% CI: 0.46, 1.01). INS/DEL was not associated with prostate cancer risk. Haplotypes containing the rs10948059 T allele were significantly associated with increased prostate cancer risk. Conclusion: In men of European descent, the GNMT rs10948059 and STRP1 were associated with prostate cancer risk. Compared to the study conducted in Taiwanese men, the susceptibility GNMT alleles for prostate cancer had a reverse relationship. This study highlights the differences in allelic frequencies and prostate cancer susceptibility in different ethnicities.

Original languageEnglish
Article numbere94683
JournalPLoS One
Volume9
Issue number5
DOIs
Publication statusPublished - May 6 2014
Externally publishedYes

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glycine N-methyltransferase
Glycine N-Methyltransferase
prostatic neoplasms
Genetic Polymorphisms
health care workers
Polymorphism
Prostatic Neoplasms
Health
genetic polymorphism
Microsatellite Repeats
Genotype
S-Adenosylhomocysteine
Sarcosine
genotype
Environmental Carcinogens
microsatellite repeats
S-Adenosylmethionine
nationalities and ethnic groups
polymorphism
confidence interval

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Genetic polymorphisms of the glycine N-methyltransferase and prostate cancer risk in the health professionals follow-up study. / Chen, Marcelo; Huang, Yi Ling; Huang, Yu Chuen; Shui, Irene M.; Giovannucci, Edward; Chen, Yen Ching; Chen, Yi Ming Arthur.

In: PLoS One, Vol. 9, No. 5, e94683, 06.05.2014.

Research output: Contribution to journalArticle

Chen, Marcelo ; Huang, Yi Ling ; Huang, Yu Chuen ; Shui, Irene M. ; Giovannucci, Edward ; Chen, Yen Ching ; Chen, Yi Ming Arthur. / Genetic polymorphisms of the glycine N-methyltransferase and prostate cancer risk in the health professionals follow-up study. In: PLoS One. 2014 ; Vol. 9, No. 5.
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abstract = "Purpose: Glycine N-methyltransferase (GNMT) affects genetic stability by regulating the ratio of S-adenosylmethionine to S-adenosylhomocysteine, by binding to folate, and by interacting with environmental carcinogens. In Taiwanese men, GNMT was found to be a tumor susceptibility gene for prostate cancer. However, the association of GNMT with prostate cancer risk in other ethnicities has not been studied. It was recently reported that sarcosine, which is regulated by GNMT, increased markedly in metastatic prostate cancer. We hereby explored the association of GNMT polymorphisms with prostate cancer risk in individuals of European descent from the Health Professionals Follow-up Study (HPFS). Methods: A total of 661 incident prostate cancer cases and 656 controls were identified from HPFS. The GNMT short tandem repeat polymorphism 1 (STRP1), 4-bp insertion/deletion polymorphisms (INS/DEL) and the single nucleotide polymorphism rs10948059 were genotyped to test for their association with prostate cancer risk. Results: The rs10948059 T/T genotype was associated with a 1.62-fold increase in prostate cancer risk (95{\%} confidence interval (CI): 1.18, 2.22) when compared with the C/C genotype. The STRP1 ≥16GAs/≥16GAs genotype was associated with decreased risk of prostate cancer when compared with the <16GAs/<16GAs genotype (odds ratio (OR) = 0.68; 95{\%} CI: 0.46, 1.01). INS/DEL was not associated with prostate cancer risk. Haplotypes containing the rs10948059 T allele were significantly associated with increased prostate cancer risk. Conclusion: In men of European descent, the GNMT rs10948059 and STRP1 were associated with prostate cancer risk. Compared to the study conducted in Taiwanese men, the susceptibility GNMT alleles for prostate cancer had a reverse relationship. This study highlights the differences in allelic frequencies and prostate cancer susceptibility in different ethnicities.",
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AU - Giovannucci, Edward

AU - Chen, Yen Ching

AU - Chen, Yi Ming Arthur

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