Jean-Nicolas Cornu1, Geraldine Cancel-Tassin2, David G Cox3, Morgan Roupret4, Nicolas Koutlidis5, Pierre Bigot6, Antoine Valeri7, Valerie Ondet8, Cécile Gaffory8, Georges Fournier7, Abdel-Rahmene Azzouzi6, Luc Cormier5, Olivier Cussenot9. 1. Academic Department of Urology, Hôpital Tenon, AP-HP, UPMC Université Paris 06, Paris, France. 2. Centre de Recherche sur les Pathologies Prostatiques et Urologiques (CeRePP), Paris, France; GRC no. 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Université Paris 06, Paris, France. 3. INSERM U1052, Cancer Research Center of Lyon, Lyon, France; Université Lyon 1, Villeurbanne, France; Centre Léon Bérard, Lyon, France. 4. Centre de Recherche sur les Pathologies Prostatiques et Urologiques (CeRePP), Paris, France; GRC no. 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Université Paris 06, Paris, France; Academic Department of Urology, Hôpital Pitié-Salpétrière, AP-HP, UPMC Université Paris 06, Paris, France. 5. Academic Department of Urology, CHU Dijon, Dijon, France. 6. Academic Department of Urology, CHU Angers, Angers, France. 7. Academic Department of Urology, CHU Brest, Brest, France. 8. Academic Department of Urology, Hôpital Tenon, AP-HP, UPMC Université Paris 06, Paris, France; Centre de Recherche sur les Pathologies Prostatiques et Urologiques (CeRePP), Paris, France; GRC no. 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Université Paris 06, Paris, France. 9. Academic Department of Urology, Hôpital Tenon, AP-HP, UPMC Université Paris 06, Paris, France; Centre de Recherche sur les Pathologies Prostatiques et Urologiques (CeRePP), Paris, France; GRC no. 5, ONCOTYPE-URO, Institut Universitaire de Cancérologie, UPMC Université Paris 06, Paris, France. Electronic address: olivier.cussenot@tnn.aphp.fr.
Abstract
UNLABELLED: Prostate-specific antigen (PSA) is still the cornerstone of prostate cancer (PCa) screening and diagnosis in both research and current clinical practice. Inaccuracy of PSA is partly due to the influence of a number of genetic, clinical, and biological factors modifying PSA blood levels. In the present study, we detailed the respective influence of each factor among age, body mass index (BMI), prostate volume, and five single-nucleotide polymorphisms-rs10788160 (10q26), rs10993994 (10q11), rs11067228 (12q24), rs17632542 (19q13.33), and rs2928679 (8p21)-on PSA values in a cohort of 1374 men without PCa. Our results show that genetic factors, when risk variants are combined, influence PSA levels with an effect size similar to that of BMI. Taken together, the respective correlations of clinical parameters and genetic parameters would make it possible to correct and adjust PSA values more effectively in each individual. These results establish the basis to understand and implement a more personalised approach for the interpretation of PSA blood levels in the context of PCa screening and diagnosis. PATIENT SUMMARY: Prostate-specific antigen (PSA) values in an individual may vary according to genetic predisposition. The effect size of this variation can be significant, comparable with those resulting from clinical characteristics. Personalised PSA testing should take this into account.
UNLABELLED: Prostate-specific antigen (PSA) is still the cornerstone of prostate cancer (PCa) screening and diagnosis in both research and current clinical practice. Inaccuracy of PSA is partly due to the influence of a number of genetic, clinical, and biological factors modifying PSA blood levels. In the present study, we detailed the respective influence of each factor among age, body mass index (BMI), prostate volume, and five single-nucleotide polymorphisms-rs10788160 (10q26), rs10993994 (10q11), rs11067228 (12q24), rs17632542 (19q13.33), and rs2928679 (8p21)-on PSA values in a cohort of 1374 men without PCa. Our results show that genetic factors, when risk variants are combined, influence PSA levels with an effect size similar to that of BMI. Taken together, the respective correlations of clinical parameters and genetic parameters would make it possible to correct and adjust PSA values more effectively in each individual. These results establish the basis to understand and implement a more personalised approach for the interpretation of PSA blood levels in the context of PCa screening and diagnosis. PATIENT SUMMARY:Prostate-specific antigen (PSA) values in an individual may vary according to genetic predisposition. The effect size of this variation can be significant, comparable with those resulting from clinical characteristics. Personalised PSA testing should take this into account.
Authors: Joseph J Otto; Vanessa L Correll; Hampus A Engstroem; Naomi L Hitefield; Brian P Main; Brenna Albracht; Teresa Johnson-Pais; Li Fang Yang; Michael Liss; Paul C Boutros; Thomas Kislinger; Robin J Leach; Oliver J Semmes; Julius O Nyalwidhe Journal: Proteomics Clin Appl Date: 2020-07-09 Impact factor: 3.494