Molecular pathways to prostate cancer.
OBJECTIVE
Prostate cancer continues to be a prevalent disease in the United States and western countries. Advances in the fields of molecular biology and genetics coupled with new developments in biotechnology have increased our understanding of events associated with the initiation and progression of prostate cancer. We reviewed recent scientific discoveries relating to genetic predisposition, somatic alterations and epigenetic phenomena involved in the pathogenesis of prostate cancer.


METHODS
Reports published in the scientific literature with relevance to the molecular biology, genetics and epigenetics of prostate cancer were identified using the MEDLINE data base. Particular emphasis was placed on articles that investigated the contribution of somatic alterations to prostate cancer.


RESULTS
A multitude of genes have recently been identified that are believed to be relevant to prostate carcinogenesis. A contemporary model for prostate cancer progression should include the potential contribution of inflammation to the development of preneoplastic or neoplastic lesions. Abnormal methylation of important growth regulatory or caretaker genes represents an alternative pathway to cancer in addition to aneuploidy, loss of heterozygosity and gene mutations.


CONCLUSIONS
The identification of molecular markers specific to early and late events in prostate cancer progression is critical for the development of improved detection and prognostication strategies. While there is evidence to support the association between inflammation and prostate cancer, the exact mechanisms by which these processes occur are not well defined. The significant contribution of somatic and epigenetic defects to prostate carcinogenesis underscores the need to develop therapeutic approaches that specifically target these molecular alterations.
Gonzalgo
Mark L
ML
James Buchanan Brady Urological Institute, The Johns Hopkins Medical Institutions, Baltimore, Maryland, USA. mgonzal@jhmi.edu
Isaacs
William B
WB
D019175:DNA Methylation; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D011471:Prostatic Neoplasms / Q000209:etiology / Q000235:genetics*
D005819:Genetic Markers