Clinic of Gynecological Surgery, Poznań University of Medical Sciences, Poznan, Poland.
Mol Biol Rep. 2012 May;39(5):5553-60. doi: 10.1007/s11033-011-1359-0. Epub 2011 Dec 20.
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.
数据表明，遗传因素单独不能解释卵巢肿瘤的发生，这表明表观遗传状态也会影响这个过程。因此，我们评估了可能影响 DNA 甲基化的基因多态性变异对波兰人群卵巢癌发病风险的贡献。我们使用 PCR-RFLP 和 HRM 分析，研究了 BHMT(rs3733890)、MTHFD1(rs2236225)、MTHFR(rs1801133)、MTR(rs1805087)、MTRR(rs1801394)和 TCN2(rs1801198)基因型和等位基因在卵巢癌患者(n=136)和对照组(n=160)中的分布。此外，我们还使用 DNA 和甲基化特异性 PCR(MSP)来确定这些患者癌组织中 Cadherin 13(CDH13)启动子的甲基化情况。我们没有观察到所有研究的基因变异与卵巢癌的发病之间存在显著关联。MTHFR Ala222Val 多态性的最低 P(趋势)=0.1226。此外，在患者组和对照组中，MTHFR Ala/Ala 与 Val/Val 和 Val/Ala 基因型的比较中，最低 P=0.0772。多维降维分析也没有表明所有分析的 SNPs 对卵巢癌的发病存在显著的交互遗传作用。然而，我们观察到大约 21%（29/136）的卵巢癌患者 CDH13 启动子频繁甲基化。我们的结果可能表明，所选的多态性基因变异可能不会导致卵巢癌的发生。
