Genetic polymorphisms of CYP17A1, vitamin D receptor and androgen receptor in Italian heredo-familial and sporadic prostate cancers

Background: Searching for genetic and environmental factors predisposing to prostate cancer, common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR genes, and the number of CAG repeats from AR were investigated in Italian heredo-familial prostate cancer (HFPC) patients controlled for dietary intake and life style habits. Methods: We evaluated differences between HFPC and sporadic cancers, in the pattern of common single-nucleotide polymorphisms in CYP17A1, CYP19A1, VDR genes, and the CAG repeat from AR, controlling for dietary intake and lifestyle habits in a regionwide population. Ninety-five patients with HFPC were identified and 378 sporadic prostate cancers were randomly selected as controls. Dietary intake and lifestyle habits were determined through self-administered questionnaires in all patients. Genotyping of polymorphisms for CYP17A1, CYP19A1, VDR, and the CAG repeat from AR was carried out using pyrosequencing. Results: HFPC cases were significantly younger than controls, whereas similar proportions of localized tumours, favourable histology, and abnormal prostate serum antigen levels (4–19 ng/ml) were detected in the two groups. A statistically evident gene–gene interaction was found: a 5-fold higher probability [odds ratio (OR) = 4.83; 95% confidence interval (CI): 1.37–17.02] of HFPC was observed in the subgroup profiling VDR1 T/T genotypes coupled with VDR2 T/T genotype. Among nutrients, an increase in HFPC risk (OR = 3.14; 95% CI: 1.12–8.81) was found only for zinc, when associated with the VDR2 T/T genotype. Conclusions: Significant evidence for positive interactions between VDR1 and VDR2 genotypes was demonstrated, suggesting that high-risk multigenic polymorphism profiles could variously sustain HFPC tumorigenesis.