Constitutional polymorphisms of prostate cancer: prognostic and diagnostic implications.
Prostate cancer is the most common cancer diagnosis in men. While often perceived as a slow, indolent malignancy, prostate cancer trails only lung cancer among cancer-related mortality in men. Current diagnosis and treatment algorithms are plagued by overdiagnosis of non-lethal indolent prostate cancer with no proven means to predict, detect, and prevent aggressive lethal prostate cancer in men most at risk. These challenges are particularly concerning for African-American men who demonstrate increased rates of prostate cancer incidence and mortality when compared to other ethnic groups. With the completion of the human genome project, technology and techniques now exist to differentiate cancer from normal tissues based on the expression patterns of thousands of genes assessed simultaneously on a single microarray gene 'chip'. This platform has greatly improved our understanding of genes that regulate tumor behavior once cancer is established. Microarrays can also be utilized in patients without cancer to determine which patients are at high risk for tumor development and in need of rational prevention strategies. Constitutional single nucleotide polymorphisms (SNPs) are one source of genetic variation and may serve as a means to identify these high-risk individuals. SNPs are single nucleotide base pair changes within a gene which occur in one percent or more of the population. SNPs can contribute to a disease state by altering the function of a protein encoded by a gene without affecting gene expression. This review will examine the current understanding of constitutional SNPs associated with prostate cancer carcinogenesis, highlight two current diagnostic array platforms and discuss implications for future prevention and screening programs.
Hahn
Noah M
NM
Indiana University Melvin & Bren Simon Cancer Center, Indiana Cancer Pavilion Room RT415, 535 Barnhill Drive, Indianapolis, Indiana 46202, USA. nhahn@iupui.edu
Kelley
Mark R
MR
Klaunig
James E
JE
Koch
Michael O
MO
Li
Lang
L
Sweeney
Christopher J
CJ
D014408:Biomarkers, Tumor / Q000235:genetics*; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000517:prevention & control; D018570:Risk Assessment
D014408:Biomarkers, Tumor