title: Genetic factors regulating inflammation and DNA methylation associated with prostate cancer.
abstract: 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-1β, 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-1β (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.
authors.affiliation: Department of Experimental Pathology, School of Medicine, University of Bologna, Bologna, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Ianni
authors.forename: E
authors.initials: E
authors.lastname: Porcellini
authors.forename: I
authors.initials: I
authors.lastname: Carbone
authors.forename: M
authors.initials: M
authors.lastname: Potenzoni
authors.forename: A M
authors.initials: AM
authors.lastname: Pieri
authors.forename: C D
authors.initials: CD
authors.lastname: Pastizzaro
authors.forename: L
authors.initials: L
authors.lastname: Benecchi
authors.forename: F
authors.initials: F
authors.lastname: Licastro
mesh_terms: D000368:Aged; D000483:Alleles; D019175:DNA Methylation / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D050938:Glycine N-Methyltransferase / Q000235:genetics; D006801:Humans; D007249:Inflammation / Q000235:genetics* / Q000473:pathology; D016753:Interleukin-10 / Q000235:genetics; D053583:Interleukin-1beta / Q000235:genetics; D008297:Male; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics; D000514:alpha 1-Antichymotrypsin / Q000235:genetics
chemical_list: D053583:Interleukin-1beta; D042461:Vascular Endothelial Growth Factor A; D000514:alpha 1-Antichymotrypsin; D016753:Interleukin-10; C494510:GNMT protein, human; D050938:Glycine N-Methyltransferase