Effects of G/A polymorphism, rs266882, in the androgen response element 1 of the PSA gene on prostate cancer risk, survival and circulating PSA levels

Abstract

Prostate-specific antigen (PSA) is a protease produced in the prostate that cleaves insulin-like growth factor binding protein-3 and other proteins. Production is mediated by the androgen receptor (AR) binding to the androgen response elements (ARE) in the promoter region of the PSA gene. Studies of a single nucleotide polymorphism (PSA À158 G/A, rs266882) in ARE1 of the PSA gene have been conflicting for risk of prostate cancer and effect on plasma PSA levels. In this nested case -control analysis of 500 white cases and 676 age-and smoking-matched white controls in the Physicians' Health Study we evaluated the association of rs266882 with risk and survival of prostate cancer and prediagnostic total and free PSA plasma levels, alone or in combination with AR CAG repeats. We used conditional logistic regression, linear regression and Cox regression, and found no significant associations between rs266882 (GG allele vs AA allele) and overall prostate cancer risk (RR ¼ 1.21, 95% confidence intervals (CI): 0.88 -1.67) or prostate cancer-specific survival (RR ¼ 0.94, 95%CI: 0.56 -1.58). Similarly, no associations were found among high grade or advanced stage tumours, or by calendar year of diagnosis. There was no significant association between rs266882 and baseline total or free PSA levels or the AR CAG repeats, nor any interaction associated with prostate cancer risk. Meta-analysis of 12 studies of rs266882 and overall prostate cancer risk was null.

Genetic polymorphism in sex hormone metabolism and prostate cancer risk

“…A significant relationship was observed between the GG genotype and BPH (P = 0.033). In the studies by Salinas et al (2005) and Jesser et al (2008), no significant difference was found in the PSA-158 G/A polymorphism for prostate cancer. However, in a meta-analysis including 12 trials, the PSA-158 G/A polymorphism had no effect on prostate cancer risk.…”

Serum level of IGFBP3 and IGF1/IGFBP3 molar ratio in addition to PSA and single nucleotide polymorphism in PSA and CYP17 gene may contribute to early diagnostics of prostate cancer

“…In addition, PSA is an IGFBP-3 protease. It cleaves IGFBP-3 [7,25], what results in an increase of free IGF-1 fraction in circulation.…”

“…In the promoter ARE-I region at the -158 position from starting point of transcription, onenucleotide polymorphism (A/G) was determined. It has been reported, this polymorphism is associated with higher PSA level and higher risk of PCa development [6,7,8].…”

Genetic polymorphisms in the human tissue kallikrein (KLK) locus and their implication in various malignant and non-malignant diseases

“…Some have reported an association with the same allele as the original study (Gsur et al , 2002 ;Medeiros et al , 2002 ;Cicek et al , 2005 ;Lai et al , 2007 ), while others have reported either a significant association in the opposite direction (Chiang et al , 2004 ;Binnie et al , 2005 ) or no association for this SNP (Wang et al , 2003 ;Salinas et al , 2005 ;Mononen et al , 2006 ;Severi et al , 2006 ;Cunningham et al , 2007 ;Pal et al , 2007 ;Penney et al , 2011 ). A meta-analysis of all studies published up until 2008 reported no evidence of association with prostate cancer risk overall (Supplementary Table 1; Jesser et al , 2008 ).…”