Low Expression Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Genotype Is Associated With Decreased Prostate Cancer Risk

BACKGROUND. Cystic fibrosis transmembrane conductance regulator(CFTR) is expressed in a wide variety of epithelial cells including theprostate duct and subglandular epithelia. Previous studies have suggestedthat CFTR mutations and polymorphisms may be associated with severalcancers. Mutations and polymorphisms in the CFTR gene are responsiblefor cystic fibrosis (CF), and the incidence of prostate cancer in CFpatients seemed to be lower than expected.OBJECTIVES. To investigate the association between CFTR genefunctional polymorphisms and prostate cancer risk.METHODS. A population-based case-control study was conductedincluding 230 prostate cancer patients and 230 age-matched controls. Weused PCR-RFLP to analysis the M470V polymorphism and PCR-STRPto analysis the IVS8-poly(T) tract in CFTR gene.RESULTS. We observed an association between the low expressionallele, IVS8-5T and reduced prostate cancer susceptibility (P=0.002;OR=0.281, 95%CI 0.120～0.658). Logistic regression analysis confirmed that the 5T/7T genotype was in protective association against prostatecancer risk (P=0.003; OR=0.232, 95%CI 0.090～0.599). Linkagedisequilibrium between IVS8-poly(T) and M470V existed amongprostate cancer patients (D'=0.701). The low expression haplotype,"5T-V470" was found to be associated with protection against prostatecancer risk (P=0.010; OR=0.324, 95%CI 0.132～0.796).CONCLUSIONS. Our results indicate that the low expression CFTRfunctional polymorphisms contribute to a reduced risk of prostate cancerin Chinese Han population, and may be a protective factor againstprostate cancer.