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PLoS One. 2014 May 6;9(5):e94683. doi: 10.1371/journal.pone.0094683. eCollection 2014.

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

Author information

  • 1Department of Urology, Mackay Memorial Hospital, Taipei, Taiwan; Department of Cosmetic Applications and Management, Mackay Junior College of Medicine, Nursing and Management, Taipei, Taiwan; School of Medicine, Mackay Medical College, New Taipei City, Taiwan.
  • 2Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
  • 3Genetics Center, Department of Medical Research, China Medical University Hospital, Taichung, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan.
  • 4Department of Epidemiology, School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
  • 5Department of Epidemiology, School of Public Health, Harvard University, Boston, Massachusetts, United States of America; Department of Nutrition, School of Public Health, Harvard University, Boston, Massachusetts, United States of America.
  • 6Department of Public Health, College of Public Health, National Taiwan University, Taipei, Taiwan; Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan; Research Center for Genes, Environment, and Human Health, College of Public Health, National Taiwan University, Taipei, Taiwan.
  • 7Department of Microbiology, School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Infectious Disease and Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan.

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.

PMID:
24800880
[PubMed - in process]
PMCID:
PMC4011739
Free PMC Article
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