Peroxisome proliferator-activated receptor-gamma polymorphism, body mass and prostate cancer risk: evidence for gene-environment interaction.
BACKGROUND
Peroxisome proliferator-activated receptor (PPAR)-gamma has been implicated in prostate cancer. In the present case-control study, we tested if a common Pro12Ala polymorphism in PPAR-gamma 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-gamma 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-gamma 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-gamma 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.
Zmuda
Joseph M
JM
Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA 15261, USA. zmudaj@edc.pitt.edu
Modugno
Francesmary
F
Weissfeld
Joel L
JL
Cauley
Jane A
JA
Trump
Donald L
DL
Moffett
Susan P
SP
Ferrell
Robert E
RE
D000328:Adult; D000368:Aged; D000409:Alanine; D015992:Body Mass Index; D016022:Case-Control Studies; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000097:blood; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D047495:PPAR gamma / Q000235:genetics*; D011110:Polymorphism, Genetic; D011237:Predictive Value of Tests; D011392:Proline; D011471:Prostatic Neoplasms / Q000097:blood / Q000453:epidemiology / Q000209:etiology* / Q000235:genetics / Q000503:physiopathology*; D049629:Waist-Hip Ratio
D007328:Insulin; D047495:PPAR gamma; D011392:Proline; D000409:Alanine