DNA methylation in prostate cancer.
Prostate cancer is the most common malignancy and the second leading cause of cancer death among men in the United States. There are three well-established risk factors for prostate cancer: age, race and family history. The molecular bases for these risk factors are unclear; however, they may be influenced by epigenetic events. Epigenetic events covalently modify chromatin and alter gene expression. Methylation of cytosine residues within CpG islands on gene promoters is a primary epigenetic event that acts to suppress gene expression. In tumorigenesis, the normal functioning of the epigenetic-regulatory system is disrupted leading to inappropriate CpG island hypermethylation and aberrant expression of a battery of genes involved in critical cellular processes. Cancer-dependent epigenetic regulation of genes involved in DNA damage repair, hormone response, cell cycle control and tumor-cell adhesion/metastasis can contribute significantly to tumor initiation, progression and metastasis and, thereby, increase prostate cancer susceptibility and risk. In this review, we will discuss current research on genes that are hypermethylated in human prostate cancer. We will also discuss the potential involvement of DNA methylation in age-related, race-related and hereditary prostate cancer, and the potential use of hypermethylated genes as biomarkers to detect prostate cancer and assess its risk.
Li
Long-Cheng
LC
Department of Urology, Veterans Affairs Medical Center, and University of California San Francisco, 4150 Clement Street, San Francisco, CA 94121, USA.
Okino
Steven T
ST
Dahiya
Rajvir
R
D000367:Age Factors; D000728:Androgens / Q000494:pharmacology; D014408:Biomarkers, Tumor / Q000032:analysis*; D002453:Cell Cycle / Q000502:physiology*; D018899:CpG Islands / Q000235:genetics; D004249:DNA Damage; D019175:DNA Methylation; D004260:DNA Repair; D004967:Estrogens / Q000494:pharmacology; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D010375:Pedigree; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000503:physiopathology*; D044469:Racial Groups; D012307:Risk Factors
D000728:Androgens; D014408:Biomarkers, Tumor; D004967:Estrogens