title: Epigenetic susceptibility factors for prostate cancer with aging.
abstract: BACKGROUND
  Increasing age is a significant risk factor for prostate cancer. The prostate is exposed to environmental and endogenous stress that may underlie this remarkable incidence. DNA methylation, genomic imprinting, and histone modifications are examples of epigenetic factors known to undergo change in the aging and cancerous prostate. In this review we examine the data linking epigenetic alterations in the prostate with aging to cancer development.
  
  
  METHODS
  An online search of current and past peer reviewed literature on epigenetic changes with cancer and aging was performed. Relevant articles were analyzed.
  
  
  RESULTS
  Epigenetic changes are responsible for modifying expression of oncogenes and tumor suppressors. Several of these changes may represent a field defect that predisposes to cancer development. Focal hypermethylation occurs at CpG islands in the promoters of certain genes including GSTP1, RARβ2, and RASSF1A with both age and cancer, while global hypomethylation is seen in prostate cancer and known to occur in the colon and other organs. A loss of genomic imprinting is responsible for biallelic expression of the well-known Insulin-like Growth Factor 2 (IGF2) gene. Loss of imprinting (LOI) at IGF2 has been documented in cancer and is also known to occur in benign aging prostate tissue marking the presence of cancer. Histone modifications have the ability to dictate chromatin structure and direct gene expression.
  
  
  CONCLUSIONS
  Epigenetic changes with aging represent molecular mechanisms to explain the increased susceptibly of the prostate to develop cancer in older men. These changes may provide an opportunity for diagnostic and chemopreventive strategies given the epigenome can be modified.
authors.affiliation: Department of Urology, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin.
authors.forename: N A
authors.initials: NA
authors.lastname: Damaschke
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.forename: S
authors.initials: S
authors.lastname: Bhusari
authors.forename: J P
authors.initials: JP
authors.lastname: Svaren
authors.forename: D F
authors.initials: DF
authors.lastname: Jarrard
mesh_terms: D000375:Aging / Q000235:genetics*; D018899:CpG Islands / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D018392:Genomic Imprinting / Q000235:genetics; D006657:Histones / Q000235:genetics; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics; D008297:Male; D011471:Prostatic Neoplasms / Q000453:epidemiology / Q000235:genetics*; D012307:Risk Factors
chemical_list: D006657:Histones; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II
keywords: aging; epigenetics; imprinting; methylation; prostate cancer