Department of Urology, Tenon Hospital, University Paris 6, Paris, France. ER2, UPMC, University Paris 6, Paris, France Centre de Recherche sur les Pathologies Prostatiques (CeRePP), Tenon Hospital, Paris, France.
Single Nucleotide Polymorphisms (SNPs) have been associated to prostate cancer (PCa) risk and tumor aggressiveness in retrospective studies. To assess value of genotyping in a clinical setting, we prospectively evaluated the correlation between three genotypes (rs1447295 and rs6983267(8q24) and rs4054823(17p12)) and prostatic biopsy outcome in a French population of Caucasian men. 598 patients with Prostatic Specific Antigen (PSA) >4ng/mL or abnormal digital rectal examination (DRE) participated in this prospective, multicentre study. Age, familial history of PCa, body mass index (BMI), data of DRE, International Prostate Symptom Score (I-PSS) score, PSA value, and prostatic volume were prospectively collected before prostatic biopsy. Correlation between genotypes and biopsy outcome (positive or negative) and Gleason score (≤ 6 or >6) were studied by univariate and multivariable analysis. Rs1447295 and rs6983267 risk variants were found to be associated with the presence of PCa in univariate analysis. Rs6983267 genotype remained significantly linked to a positive biopsy (OR=1.66, 95%CI:1.06-2.59, p=0.026) in multivariable analysis, but rs1447295 genotype did not (OR=1.47, 95%CI: 0.89-2.43, p=0.13). When biopsy outcome was stratified according to Gleason score, risk variants of rs1447295 were associated with aggressive disease (Gleason score ≥ 7) in univariate and multivariable analysis (OR=2.05 95%CI: 1.10-3.79, p=0.023). rs6983267 GG genotype was not related to aggressiveness. The results did not reach significance concerning rs4054823 for any analysis. This inaugural prospective evaluation thus confirmed potential usefulness of genotyping PCa assessment. Ongoing clinical evaluation of larger panels of SNPs will detail the actual impact of genetic markers on clinical practice.
Written by:
Cornu JN, Drouin S, Cancel-Tassin G, Bigot P, Azzouzi AR, Koutlidis N, Cormier L, Gaffory C, Rouprêt M, Sèbe P, Bitker MO, Haab F, Cussenot O.
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Reference: Mol Med. 2011 Feb 4. Epub ahead of print.
PubMed Abstract
PMID: 21308149
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