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Erschienen in: Medical Oncology 1/2013

01.03.2013 | Original Paper

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

verfasst von: Cátia Monteiro, Marta Velho Sousa, Ricardo Ribeiro, Joaquina Maurício, Avelino Fraga, Rui Medeiros

Erschienen in: Medical Oncology | Ausgabe 1/2013

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Abstract

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.
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Metadaten
Titel
Genetic variants in AR and SHBG and resistance to hormonal castration in prostate cancer
verfasst von
Cátia Monteiro
Marta Velho Sousa
Ricardo Ribeiro
Joaquina Maurício
Avelino Fraga
Rui Medeiros
Publikationsdatum
01.03.2013
Verlag
Springer US
Erschienen in
Medical Oncology / Ausgabe 1/2013
Print ISSN: 1357-0560
Elektronische ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-013-0490-2

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