Journal of Clinical Oncology  
Search for:
Limit by:
  Browse by Subject or Issue
Home Search or Browse JCO Subscriptions PDA Services My JCO Customer Service

Journal of Clinical Oncology, Vol 26, No 6 (February 20), 2008: pp. 842-847
© 2008 American Society of Clinical Oncology.
DOI: 10.1200/JCO.2007.13.6804

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a colleague
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Save to my personal folders
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Google Scholar
Right arrow Articles by Ross, R. W.
Right arrow Articles by Freedman, M.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ross, R. W.
Right arrow Articles by Freedman, M.

Inherited Variation in the Androgen Pathway Is Associated With the Efficacy of Androgen-Deprivation Therapy in Men With Prostate Cancer

Robert W. Ross, William K. Oh, Wanling Xie, Mark Pomerantz, Mari Nakabayashi, Oliver Sartor, Mary-Ellen Taplin, Meredith M. Regan, Philip W. Kantoff, Matthew Freedman

From the Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA

Corresponding author: Matthew Freedman, MD, Dana-Farber Cancer Institute, Dana 710-C, 44 Binney St, Boston, MA 02115; e-mail: freedman{at}broad.mit.edu

Purpose: Androgen-deprivation therapy (ADT) is the most common and effective systemic therapy for advanced prostate cancer. We hypothesized that germline genetic variation in the androgen axis would improve the efficacy of ADT.

Patients and Methods: A cohort of 529 men with advanced prostate cancer treated with ADT was genotyped for 129 DNA polymorphisms distributed across 20 genes involved in androgen metabolism.

Results: Three polymorphisms in separate genes (CYP19A1, HSD3B1, and HSD17B4) were significantly (P < .01) associated with time to progression (TTP) during ADT, remaining so in multivariate analyses and after correcting for the number of hypotheses tested. Individuals carrying more than one of the polymorphisms associated with improved TTP demonstrated a better response to therapy than individuals carrying zero or one (P < .0001).

Conclusion: This report is the first to examine the influence of inherited variation in the androgen metabolic pathway on the efficacy of ADT, establishing the importance of pharmacogenomics on individual's response to this therapy. At least two potential clinical benefits may be realized from this study. The first is prognostic –genotyping patients at these loci may yield important information that could improve efficacy prediction. The second is therapeutic –these results shed light on the pathways that govern response to ADT. Drugs could be developed (or may already exist) to inhibit or augment these targets to improve ADT efficacy.

Supported by a Dunkin Donuts Rising Star Award (R.W.R.), the Gelb Center for Translational Research (P.W.K., W.K.O.), Bing Sound Wong Fund for Prostate Cancer Research (W.K.O.) and the Dana-Farber/Harvard Cancer Center Prostate Cancer SPORE (National Cancer Institute Grant No. 5P50CA90381). The Broad Institute Center for Genotyping and Analysis is supported by Grant No. U54 RR020278-01 from the National Center for Research Resources.

P.W.K. and M.F. contributed equally to this work.

Presented in part at the American Society of Clinical Oncology Prostate Cancer Symposium, February 22-24, 2007, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.




This article has been cited by other articles:


Home page
JWatch Oncology and HematologyHome page
Insights into the Pharmacogenomics of Hormonal Therapy for Advanced Prostate Cancer
Journal Watch Oncology and Hematology, March 18, 2008; 2008(318): 5 - 5.
[Full Text]



About
JCO
 Editorial
Roster
 Advertising
Information
 Librarians &
Institutions
 Rights &
Permissions
 Site Map

Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
Terms and Conditions of Use
  HighWire Press HighWire Press™ assists in the publication of JCO Online