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

• Published in: Molecular biology reports 2012-05, Vol.39 (5), p.5553-5560
• Main Authors: Pawlik, Piotr, Mostowska, Adrianna, Lianeri, Margarita, Sajdak, Stefan, Kędzia, Helena, Jagodzinski, Paweł P.
• Format: Article
• Language: English
• Subjects: Animal Anatomy; Animal Biochemistry; Betaine-homocysteine S-methyltransferase; Biomedical and Life Sciences; Cadherin; Cadherins - genetics; Case-Control Studies; Choline; Choline - metabolism; Data processing; Databases, Genetic; DNA; DNA methylation; DNA Methylation - genetics; epigenetics; Epistasis, Genetic; Female; Folic acid; Folic Acid - metabolism; Gene Frequency - genetics; Gene polymorphism; Genes, Neoplasm; Genetic effects; Genetic factors; Genetic Predisposition to Disease; Genotype & phenotype; Genotypes; Histology; Humans; Incidence; Life Sciences; Metabolic Networks and Pathways - genetics; Metabolism; Methylenetetrahydrofolate reductase; Middle Aged; Molecular biology; Morphology; Ovarian cancer; Ovarian carcinoma; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - genetics; Poland - epidemiology; Polymerase chain reaction; Polymorphism, Single Nucleotide - genetics; Population genetics; Promoter Regions, Genetic - genetics; Promoters; Restriction fragment length polymorphism; Risk Factors; Single-nucleotide polymorphism; Tumorigenesis
• ISSN: 0301-4851; 1573-4978
• DOI: 10.1007/s11033-011-1359-0

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 P trend  = 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.