Folate and choline metabolism gene variants and development of uterine cervical carcinoma

Clin Biochem. 2011 Jun;44(8-9):596-600. doi: 10.1016/j.clinbiochem.2011.02.007. Epub 2011 Feb 22.

Abstract

Objective: It has been reported that aberrant DNA methylation can be associated with HPV infection and cervical tumorigenesis. The aim of this study was to evaluate the possibility that polymorphic variants of genes that may affect DNA methylation status are associated with the risk of cervical cancer in the Polish population.

Design and method: Employing PCR-RFLPs and HRM analyses, we examined the prevalence of BHMT Arg239Gln (rs3733890), MTR Asp919Gly (rs1805087), MTHFR Ala222Val (rs1801133), MTHFD1 Arg653Gln (rs2236225) and MTRR Ile22Met (rs1801394) genotypes and alleles in patients with advanced cervical cancer (n=124) and controls (n=168).

Results: The odds ratio (OR) for BHMT Gln/Gln genotype was 0.433 (95% CI=0.1780-1.054; p=0.0602). The OR for patients having the BHMT Arg/Gln or Gln/Gln genotypes was 0.579 (95% CI=0.3622-0.924; p=0.0216). We also observed a significantly higher frequency of the BHMT 239Gln allele in controls than in patients, p=0.0165. The genotype and allele frequencies of the MTR Asp919Gly, MTHFR Ala222Val, MTHFD1 Arg653Gln and MTRR Ile22Met gene variants did not display statistical differences between patients with cervical cancer and controls. We also did not find a significant association between the distribution of any genotypes or alleles and cancer characteristics.

Conclusion: Our results might suggest the protective role of the BHMT 239Gln variant in cervical cancer incidence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 5,10-Methylenetetrahydrofolate Reductase (FADH2) / genetics
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / genetics
  • Adult
  • Alleles
  • Betaine-Homocysteine S-Methyltransferase / genetics
  • Choline / genetics*
  • Female
  • Ferredoxin-NADP Reductase / genetics
  • Folic Acid / genetics*
  • Genotype
  • Humans
  • Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics
  • Middle Aged
  • Minor Histocompatibility Antigens
  • Models, Biological
  • Odds Ratio
  • Polymerase Chain Reaction
  • Polymorphism, Restriction Fragment Length
  • Polymorphism, Single Nucleotide / genetics
  • Uterine Cervical Neoplasms / genetics*

Substances

  • Minor Histocompatibility Antigens
  • Folic Acid
  • methionine synthase reductase
  • Ferredoxin-NADP Reductase
  • 5,10-Methylenetetrahydrofolate Reductase (FADH2)
  • MTHFD1 protein, human
  • Methylenetetrahydrofolate Dehydrogenase (NADP)
  • 5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase
  • BHMT protein, human
  • Betaine-Homocysteine S-Methyltransferase
  • Choline