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 Ke ˛dzia • Pawel P. Jagodzinski Received: 21 July 2011 / Accepted: 12 December 2011 / Published online: 20 December 2011 Ó Springer Science+Business Media B.V. 2011 Abstract Data indicates that genetic factors alone do not account for ovarian tumorigenesis, suggesting that epige- netic 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). More- over, 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. Keywords Ovarian cancer Á Polymorphism Á Choline Á Folate metabolism Introduction Ovarian cancer is the one of the leading causes of malig- nant deaths in women in Europe and United States [1, 2]. Ovarian carcinogenesis remains unclear, though there is much evidence showing a decreased risk for ovarian cancer in women who use oral contraceptives, have greater parity, or breastfed long-term [3]. In contrast, an increased risk for ovarian cancer can be associated with environmental or inflammatory factors and a few significant-risk genetic components, such as high-penetrance genes (e.g., BRCA1) [3]. However, the genetic factors alone have been shown to be insufficient for ovarian carcinogenesis, suggesting the importance of changes in epigenetic status for both ovarian tumorigenesis and the development of other cancers [4–7]. Epigenetic changes include heritable alterations in gene expression that do not affect the DNA sequence. These changes encompass DNA methylation, covalent modifica- tion of histones, repositioning of nucleosomes, and micro- RNAs affecting posttranscriptional gene regulation [8, 9]. The transport of a methyl group to the carbon-5 position of cytosines within cytosine-guanine dinucleotides (CpG Electronic supplementary material The online version of this article (doi:10.1007/s11033-011-1359-0) contains supplementary material, which is available to authorized users. P. Pawlik Á S. Sajdak Clinic of Gynecological Surgery, Poznan ´ University of Medical Sciences, Poznan, Poland A. Mostowska Á M. Lianeri Á P. P. Jagodzinski (&) Department of Biochemistry and Molecular Biology, Poznan ´ University of Medical Sciences, 6 S ´ wie ˛cickiego St., 60-781 Poznan, Poland e-mail: pjagodzi@um.poznan.pl H. Ke ˛dzia Department of Pathology, Poznan ´ University of Medical Sciences, Poznan, Poland 123 Mol Biol Rep (2012) 39:5553–5560 DOI 10.1007/s11033-011-1359-0