Genetic factors regulating inflammation and DNA methylation associated with prostate cancer

Background: Prostate cancer (PCa) displays a strong familiarity component and genetic factors; genes regulating inflammation may have a pivotal role in the disease. Epigenetic changes control chromosomal integrity, gene functions and ultimately carcinogenesis. The enzyme glycine- N -methyltransferase ( GNMT ) contributes to S-adenosylmethionine level regulation and, by affecting DNA methylation, influences gene expression. The genotype and allele distribution of single-nucleotide polymorphisms (SNPs) in the promoter regions of vascular endothelial growth factor ( VEGF ), interleukin ( IL ) -10 , IL-1 β, alpha-1-antichymotrypsin ( ACT ) and GNMT genes, the level of global DNA methylation and the influence of GNMT SNP upon DNA methylation in a PCa case–control study have been investigated. Methods: SNPs of VEGF (rs699947), ACT (rs1884082), IL-1 β (rs16944), IL-10 (rs1800896) and GNMT (rs9462856) genes were assessed by PCR or by real-time PCR methods. DNA methylation was assessed by an ELISA assay. Results: Frequencies of the VEGF AA genotype, the IL-10 A allele and GNMT T allele were higher in PCa. The concomitant presence of the AA genotype of VEGF , the A allele of IL-10 and T allele of GNMT increased the risk of PCa. Total DNA methylation was decreased in PCa; control GNMT T carriers (T+) showed the highest level of DNA methylation. Conclusions: SNPs in VEGF , IL-10 and GNMT genes might have a synergistic role in the development of PCa. The GNMT T allele may influence PCa risk by affecting DNA methylation and prostate gene expression. Our observations might help implement the screening of unaffected subjects with an increased susceptibility to develop PCa.