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.