Molecular Biology Reports

, Volume 39, Issue 5, pp 5553–5560 | Cite as

Folate and choline metabolism gene variants in relation to ovarian cancer risk in the Polish population

  • Piotr Pawlik
  • Adrianna Mostowska
  • Margarita Lianeri
  • Stefan Sajdak
  • Helena Kędzia
  • Paweł P. Jagodzinski
Article

Abstract

Data indicates that genetic factors alone do not account for ovarian tumorigenesis, suggesting that epigenetic status additionally affects this process. Therefore, we assessed the possible contribution of polymorphic variants of genes that may affect DNA methylation to the risk of ovarian cancer incidence in the Polish population. Using PCR-RFLP and HRM analyses, we studied the distribution of BHMT (rs3733890), MTHFD1 (rs2236225), MTHFR (rs1801133), MTR (rs1805087), MTRR (rs1801394) and TCN2 (rs1801198) genotypes and alleles in patients with ovarian cancer (n = 136) and controls (n = 160). Moreover, using DNA and methylation-specific PCR (MSP) we also determined the methylation of the Cadherin 13(CDH13) promoter in cancerous tissue from these patients. We did not observe a significant association between all studied gene variants and the incidence of ovarian cancer. The lowest Ptrend = 0.1226 was observed for the MTHFR Ala222Val polymorphism. Moreover, the lowest P = 0.0772 was found in the comparison of MTHFR Ala/Ala versus Val/Val and Val/Ala genotypes in patients and control groups. The multifactor dimensionality reduction analysis also did not indicate a significant interactive genetic effect on ovarian cancer incidence for all analyzed SNPs. However, we observed frequent methylation of the CDH13 promoter in approximately 21% (29/136) patients with ovarian carcinomas. Our results might suggest that the selected polymorphic gene variants may not contribute to ovarian cancer incidence.

Keywords

Ovarian cancer Polymorphism Choline Folate metabolism 

Notes

Acknowledgments

Supported by grant No. 502-01-01124182-07474, Poznan University of Medical Sciences. The technical assistance of Ms. Joanna Grzelczak and Longina Nowak is gratefully acknowledged.

Supplementary material

11033_2011_1359_MOESM1_ESM.tif (33.2 mb)
Figure 1S. Contribution of six folate and choline metabolism enzymes to DNA methylation. Enzyme abbreviations: BHMT, betaine-homocysteine methyltransferase; DNMTs, MTHFD1, methylenetetrahydrofolate dehydrogenase 1; MTHFR, 5,10-methylenetetrahydrofolate reductase; MTR, 5-methyltetrahydrofolate-homocysteine methyltransferase; MTRR, methionine synthase reductase; TCN2, transcobalamin II. Substrate abbreviations: AdoHcy, S-adenosylhomocysteine; AdoMet, S-adenosylmethionine; 5,10-CH2-THF, 5,10-methylenetetrahydrofolate; 5-CH3-THF, 5-metylotetrahydrofolate; DMG, dimethylglycine; HCY, homocysteine; MET, methionine; THF, tetrahydrofolate. (TIFF 33985 kb)
11033_2011_1359_MOESM2_ESM.doc (40 kb)
Supplementary material 2 (DOC 40 kb)

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Copyright information

© Springer Science+Business Media B.V. 2011

Authors and Affiliations

  • Piotr Pawlik
    • 1
  • Adrianna Mostowska
    • 2
  • Margarita Lianeri
    • 2
  • Stefan Sajdak
    • 1
  • Helena Kędzia
    • 3
  • Paweł P. Jagodzinski
    • 2
  1. 1.Clinic of Gynecological SurgeryPoznań University of Medical SciencesPoznanPoland
  2. 2.Department of Biochemistry and Molecular BiologyPoznań University of Medical SciencesPoznanPoland
  3. 3.Department of PathologyPoznań University of Medical SciencesPoznanPoland

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