Genetic variants in AR and SHBG and resistance to hormonal castration in prostate cancer

• Type: Article in International Scientific Journal
• Date: 2013

Authors

Catia Monteiro (Author) Other; Marta Velho Sousa (Author) Other; Ricardo Ribeiro (Author) Other; Joaquina Mauricio (Author) Other; Avelino Fraga (Author) Other; Rui Medeiros (Author) ICBAS

Journal

Title: Medical Oncology

Vol. 30

ISSN: 1357-0560

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 6 Citations

Scientific classification

FOS: Medical and Health sciences > Clinical medicine

Other information

Authenticus ID: P-005-2S9

DOI: 10.1007/s12032-013-0490-2

Abstract (EN): Castration resistance is a life-threatening event that may develop in prostate cancer patients with advanced disease following hormonal castration therapy (HCT). Current understanding of the molecular mechanisms behind resistance to hormonal castration suggests a role for androgen receptor signaling and bioavailability of androgens. We evaluated whether common functional polymorphisms in AR and SHBG genes associate with response to HCT. The study included 203 prostate cancer patients with advanced disease treated with hormonal castration. Genomic DNA was isolated from whole blood, and the genetic polymorphisms AR +1733 G>A and SHBG +5790 G>A were determined by real-time PCR. Genetic variants were associated with response to treatment and time to resistance to hormonal castration. Multivariate analysis showed increased risk of developing resistance to hormonal castration in homozygous GG carriers of the SHBG +5790 G>A (HR = 1.9, 95 % CI 1.1-3.3, P = 0.019) polymorphism alone and when functionally combined with AR +1733 G>A into a high AR pathway activation genetic profile (HR = 1.9, 95 % CI 1.1-3.1, P = 0.015), after adjustment for age, PSA, Gleason's score and clinical stage. Our results suggest that the SHBG +5790 G>A polymorphism may be a useful marker to include in the pharmacogenomic profile of prostate cancer resistant to hormonal castration.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 5