Clinical Study

Peroxisome Proliferator-Activated Receptor- Polymorphism, Body Mass and Prostate Cancer Risk: Evidence for Gene-Environment Interaction
Joseph M. Zmuda^{a, c}, Francesmary Modugno^{a, c}, Joel L. Weissfeld^{a, c}, Jane A. Cauley^a, Donald L. Trump^d, Susan P. Moffett^a, Robert E. Ferrell^b

Departments of
^aEpidemiology and
^bHuman Genetics, Graduate School of Public Health, University of Pittsburgh, and the
^cUniversity of Pittsburgh Cancer Institute, Pittsburgh, Pa., and
^dDepartment of Medicine, Roswell Park Cancer Institute, Buffalo, N.Y., USA

Address of Corresponding Author

Oncology 2006;70:185-189 (DOI: 10.1159/000093805)

  Key Words

• Genetics
• Obesity
• Polymorphism
• PPAR-
• Prostate cancer

  Abstract

Background: Peroxisome proliferator-activated receptor (PPAR)- has been implicated in prostate cancer. In the present case-control study, we tested if a common Pro¹²Ala polymorphism in PPAR- is associated with the risk of prostate cancer. Methods: Ninety-one adult Caucasians with prostate cancer were recruited between 1994 and 1998. Blood samples were also obtained from 237 community-based Caucasian men without prostate cancer. Results: Twenty-six percent of cases and 19% of controls carried at least one Ala allele (p = 0.16). There was a significant interaction between the PPAR- polymorphism and body mass index (BMI) in age-adjusted analyses (p < 0.05). Among the subgroup of men with BMI above 27.2 kg/m² (median in controls), carriers of the Ala allele had over 2-fold greater risk of prostate cancer compared to those with the Pro¹²Pro genotype (odds ratio, OR: 2.77; 95% confidence interval, CI: 1.25-6.16). No association was observed between the PPAR- genotype and prostate cancer among men with BMI below the median (OR: 0.68; 95% CI: 0.23-1.97). Conclusions: Our results suggest a novel gene-environment interaction between the PPAR- Pro¹²Ala polymorphism and body mass in prostate cancer. Further research, particularly prospective studies, is needed to confirm these findings and to clarify the underlying mechanisms involved.

Copyright © 2006 S. Karger AG, Basel

  Author Contacts

Assist. Prof. Joseph M. Zmuda
Department of Epidemiology, Graduate School of Public Health
University of Pittsburgh, 130 DeSoto Street
Pittsburgh, PA 15261 (USA)
Tel. +1 412 624 2970, Fax +1 412 624 7397, E-Mail zmudaj@edc.pitt.edu

  Article Information

Supported in part by United States Public Health Service grants AR-35582, DK-46204, 1P60 AR44811, R25-CA57703-06A1, and K07-CA80668.

Received: April 1, 2005
Accepted after revision: February 25, 2006
Published online: June 7, 2006
Number of Print Pages : 5
Number of Figures : 0, Number of Tables : 3, Number of References : 27