The Role of Genetic Markers in the Management of Prostate Cancer

• Published in: European urology 2012-10, Vol.62 (4), p.577-587
• Main Authors: Choudhury, Atish D, Eeles, Rosalind, Freedland, Stephen J, Isaacs, William B, Pomerantz, Mark M, Schalken, Jack A, Tammela, Teuvo L.J, Visakorpi, Tapio
• Format: Article
• Language: English
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - genetics; Adenocarcinoma - therapy; Animals; Biological and medical sciences; Biomarkers, Tumor - analysis; Biomarkers, Tumor - genetics; Disease Progression; Gene expression; Gene Expression Regulation, Neoplastic; Genetic Markers; Genome-Wide Association Study; GWAS; Gynecology. Andrology. Obstetrics; Humans; Male; Male genital diseases; Medical sciences; Mice; Nephrology. Urinary tract diseases; Predictive markers; Prognosis; Prognostic markers; Prostate cancer; Prostate-Specific Antigen - genetics; Prostatic Neoplasms - diagnosis; Prostatic Neoplasms - genetics; Prostatic Neoplasms - therapy; Screening; Treatment Outcome; Tumors; Tumors of the urinary system; Urinary tract. Prostate gland; Urology
• ISSN: 0302-2838; 1873-7560
• DOI: 10.1016/j.eururo.2012.05.054

Abstract Context Despite widespread screening for prostate cancer (PCa) and major advances in the treatment of metastatic disease, PCa remains the second most common cause of cancer death for men in the Western world. In addition, the use of prostate-specific antigen testing has led to the diagnosis of many potentially indolent cancers, and aggressive treatment of these cancers has caused significant morbidity without clinical benefit in many cases. The recent discoveries of inherited and acquired genetic markers associated with PCa initiation and progression provide an opportunity to apply these findings to guide clinical decision making. Objective In this review, we discuss the potential use of genetic markers to better define groups of men at high risk of developing PCa, to improve screening techniques, to discriminate indolent versus aggressive disease, and to improve therapeutic strategies in patients with advanced disease. Evidence acquisition PubMed-based literature searches and abstracts through January 2012 provided the basis for this literature review. We also examined secondary sources from reference lists of retrieved articles and data presented at recent congresses. Cited review articles are only from the years 2007–2012, favoring more recent discussions because of the rapidly changing field. Original research articles were curated based on favoring large sample sizes, independent validation, frequent citations, and basic science directly related to potentially clinically relevant prognostic or predictive markers. In addition, all authors on the manuscript evaluated and interpreted the data acquired. Evidence synthesis We address the use of inherited genetic variants to assess risk of PCa development, risk of advanced disease, and duration of response to hormonal therapies. The potential for using urine measurements such as prostate cancer antigen 3 ( PCA3 ) RNA and the transmembrane protease, serine 2 v-ets erythroblastosis virus E26 oncogene homolog (avian) ( TMPRSS2-ERG ) gene fusion to aid screening is discussed. Multiple groups have developed gene expression signatures from primary prostate tumors correlating with poor prognosis, and attempts to improve and standardize these signatures as diagnostic tests are presented. Massive sequencing efforts are underway to define important somatic genetic alterations (amplifications, deletions, point mutations, translocations) in PCa, and these alterations hold great promise as prognostic markers an