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American Journal of Epidemiology Advance Access published online on August 24, 2006
American Journal of Epidemiology, doi:10.1093/aje/kwj294
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American Journal of Epidemiology Copyright © 2006 by the Johns Hopkins Bloomberg School of Public Health All rights reserved; printed in U.S.A.
Received November 23, 2005
Accepted April 13, 2006

ORIGINAL CONTRIBUTIONS

Nonsteroidal Antiinflammatory Drugs and Decreased Risk of Advanced Prostate Cancer: Modification by Lymphotoxin Alpha

Xin Liu 1, Sarah J. Plummer 2, Nora L. Nock 3, Graham Casey 2, and John S. Witte 1 *

1 Department of Epidemiology and Biostatistics and Center for Human Genetics, University of California, San Francisco, San Francisco, CA
2 Department of Cancer Biology, Lerner Research Institute, The Cleveland Clinic Foundation, Cleveland, OH
3 Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, OH

* To whom correspondence should be addressed.
John S. Witte, E-mail: wittej{at}humgen.ucsf.edu


  Abstract

The potentially protective effect of nonsteroidal antiinflammatory drugs (NSAIDs) on prostate cancer may only exist among certain subgroups of men, such as those with particular variants in inflammatory response genes. To investigate this, the authors undertook a case-control study (n = 1,012) of the association between NSAIDs and more advanced prostate cancer in Ohio men recruited between 2001 and 2004 and evaluated whether this association was modified by a functional polymorphism in the lymphotoxin alpha (LTA) gene (LTA C+80A, where the CC genotype results in higher LTA production). The authors observed an inverse association between aspirin or ibuprofen use and disease (odds ratio = 0.67, 95% confidence interval: 0.52, 0.87). This was modified by the LTA C+80A variant (p for interaction = 0.03): Among men with the CC genotype, the inverse association between NSAIDs and prostate cancer was substantially stronger (odds ratio = 0.43, 95% confidence interval: 0.28, 0.67). For men without the CC genotype, NSAID use was not associated with disease (p = 0.30). The authors observed similar associations when examining dose/duration of NSAID use. This suggests that any potential chemoprevention of prostate cancer by NSAIDs may be most appropriate for men with the LTA +80CC genotype.

Keywords: anti-inflammatory drugs, non-steroidal; case-control studies; lymphotoxin; prostatic neoplasms.
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