The role of caveolin-1 and endothelial nitric oxide synthase polymorphisms in susceptibility to prostate cancer

Abstract

Caveolin-1(cav-1) is overexpressed in prostate cancer (PC) and is associated with progression of the disease. We investigated the effects of CAV1-T29107A and endothelial nitric oxide synthase (eNOS) G894T polymorphisms on the serum levels of testosterone, NO and prostate-specific antigen (PSA) in patients with PC. We genotyped cav-1 and eNOS genes in 112 PC patients and 150 healthy controls by PCR-RFLP. Serum levels of ${\text{NO}}_2^{-}$ and ${\text{NO}}_3^{-}$ were measured using spectrophotometry, and serum levels of testosterone and PSA were measured by ELISA. The frequencies of CAV1 genotypes A/T vs. A/A according to the dominant model AT + TT vs. AA genotype and T allele were significantly higher in PC patients in comparison with the control group and considerably increased the risk of disease by 2.19-, 1.44- and 1.6-fold, respectively. AT + TT genotypes were associated significantly with the increased risk of PC in those with smoking or diabetes by 3.08-fold (P = .004). Individuals carrying concurrently the T allele of CAV1 A29107T and the T allele of eNOS G894T genes had a significantly increased risk of PC by 2.52-fold (P = .009). We did not find any significant relationship between eNOS G894T genotypes and alleles with susceptibility to PC. Our results highlighted the significance of CAV1-T29107A SNP but not (eNOS) G894T in the susceptibility to PC in our the population that we have studied.

Keywords: PSA; caveolin-1; diabetes; eNOS; prostate cancer; smoking; testosterone.

FIGURE 1

The 2.5% agarose gel electrophoresis patterns for genotypes of CavA29107T SNP after amplification by TARMS PCR. Lane A is heterozygous mutant (A/T); Lanes C, wild genotype (A/A); Lane B, homozygous mutant (T/T); and the first lane demonstrates the 50‐bp DNA ladder

FIGURE 2

The 2.5% agarose gel electrophoresis patterns for eNOS G894T gene polymorphism alleles analysed by PCR–RFLP. Lane 1: 50‐bp DNA Ladder; Lanes 2 and 7: TT homozygous genotype; Lanes 3 and 5: GT heterozygous genotype; Lane 6: GG homozygous genotype

FIGURE 3

(a) The sequencing results of CavA29107T polymorphism: (A) wild genotype (AA); (B) heterozygote genotype (AT); (C) homozygous mutant genotype (TT), (b) sequencing results of eNOS G894T polymorphism: (A) wild genotype (GG); (B) heterozygote genotype (GT); (C) homozygous mutant genotype (TT)