Peroxisome Proliferator-Activated Receptor-γ Polymorphism, Body Mass and Prostate Cancer Risk: Evidence for Gene-Environment Interaction

Abstract

Background: Peroxisome proliferator-activated receptor (PPAR)-γ has been implicated in prostate cancer. In the present case-control study, we tested if a common Pro¹²Ala polymorphism in PPAR-γ 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-γ 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-γ 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-γ 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.