You have accessJournal of UrologyProstate Cancer: Markers II1 Apr 20122238 SINGLE NUCLEOTIDE POLYMORPHISMS ARE ASSOCIATED WITH VARIATION OF PSA LEVELS IN A CONTROL POPULATION Jean-Nicolas Cornu, Christophe Egrot, Philippe Sèbe, François Haab, Géraldine Cancel-Tassin, and Olivier Cussenot Jean-Nicolas CornuJean-Nicolas Cornu PARIS, France More articles by this author , Christophe EgrotChristophe Egrot PARIS, France More articles by this author , Philippe SèbePhilippe Sèbe PARIS, France More articles by this author , François HaabFrançois Haab PARIS, France More articles by this author , Géraldine Cancel-TassinGéraldine Cancel-Tassin PARIS, France More articles by this author , and Olivier CussenotOlivier Cussenot PARIS, France More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.2414AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Genome wide association studies have provided evidence that some single nucleotide polymorphisms are associated with a higher risk of prostate cancer. A few preliminary studies have suggested a link between some single nucleotide polymorphisms (SNPs) and PSA levels. Such an association could be useful to “adjust” PSA values in order to avoid unnecessary biopsies, but data about these associations remain scarce. Our goal was to assess the correlation between SNPs located in genes implicated in steroid hormone metabolism and PSA levels in a population of control patients. METHODS A study on 727 men free of personal and familial prostate cancer history were included after written informed consent for genetic analysis. All patients were Caucasians. For all patients, genotypes of 126 SNPs located in genes implicated in steroid hormone metabolism were directly assessed by Taqman analysis. Influence of each SNP on PSA values after adjusting for age and body mass index (BMI) was assessed in univariate analysis by analysis of covariance (ANCOVA). The SNPs significantly associated with prostate volume were then included in a multivariate analysis model. RESULTS Three SNPs located in genes implicated in steroid hormone metabolism were significantly associated with a higher or a lower prostate volume. Namely, rs2735839, rs10993994 and rs2391671 were significantly associated with a significant decrease in PSA values inunivariate analysis after adjusting for age and BMI (p=0.0004, 0.046, and 0.012 respectively). These three SNPs are located respectively in the PSA (KLK3) gene, Microseminoprotein-beta (MSMB) gene, and Cyclic-AMP responsive element binding protein 5 (CREB5). These results were maintained after multivariate analysis with a similar level of significance, indicating their independent association with prostate volume. The power of the association of each SNP with prostate volume was comparable to the effect of age. Our study is limited by the absence of accurate evaluation of the prostate weight, that could be a confounding factor, even if age is included in our study. CONCLUSIONS Some genetic variants of steroid hormones metabolism and pathway genes are linked to a higher prostate volume. In particular, the implications of CREB5 indicate that the pathway of protein kinase A may be implicated in PSA modifications. The estrogen pathway seems implicated, legitimizing deeper studies to further assess the role of ESR-1 in BPH pathogenesis. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e902-e903 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jean-Nicolas Cornu PARIS, France More articles by this author Christophe Egrot PARIS, France More articles by this author Philippe Sèbe PARIS, France More articles by this author François Haab PARIS, France More articles by this author Géraldine Cancel-Tassin PARIS, France More articles by this author Olivier Cussenot PARIS, France More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...