Novel polymorphisms of prostate-specific antigen (PSA) gene associated with PSA mRNA expression in breast cancer

Abstract

A growing body of evidence suggests that prostate-specific antigen (PSA) is a novel prognostic factor for breast cancer. The molecular mechanism of variant PSA expression in breast cancer has remained poorly understood in spite of intensive research. Previous studies have shown that the coding region of the PSA gene is not a target for mutations in prostate cancer and breast cancer. The purpose of this study was to analyze genetic variations in the promoter region of the PSA gene, and to detect whether such variations are correlated with PSA mRNA expression in breast tumors. We identified two polymorphisms in the proximal promoter region of the PSA gene. These polymorphisms are located at positions Ϫ252 (G or A) and Ϫ205 (A or AA), and generate three genotypes. The genotypes were associated with PSA mRNA expression. Our findings suggest that these polymorphisms identified in the proximal promoter region may affect the transcriptional activity of PSA.

Genetic Susceptibility to Prostate Cancer: Prostate-specific Antigen and its Interaction with the Androgen Receptor (United States)

“…The )252 A allele was always in phase with )205 AA whereas the )252 G allele was always linked with )205 A, confirming a previous report [17] of complete LD between the )252 and )205 polymorphisms. We did not observe a deletion polymorphism (DA) at position )232, and were unable to confirm a previous report [18] of perfect LD between the )252 G and putative )232 DA allele.…”

“…The proximal region of the PSA promoter contains ARE I and ARE II, centered at )170 bp and )394 bp, respectively [12,13]. Two single nucleotide polymorphisms (SNPs) have been described in the proximal PSA promoter: a G/A transition at position )158 in ARE I [16] and a G/A transition at position )252, that are not in complete linkage disequilibrium [17,18].…”

Profiling Genetic Variation along the Androgen Biosynthesis and Metabolism Pathways Implicates Several Single Nucleotide Polymorphisms and Their Combinations as Prostate Cancer Risk Factors

“…From the detected variants, 14 changed the protein sequence (SRD5A2 A49T, SRD5A2 V89L, HSD3B1 N367T, HSD3B1 R71I, HSD17B2 A111T, HSD17B3 G289S, AKR1C3 Q5H, AKR1C3 P180S, CYP19A1 R264C, KLK3 D102N, KLK3 L132I, KLK3 I179T, CYP19A1 T201M, HSD17B3 729_735 delGA-TAACC). These and two found noncoding variants (CYP17A1 À34T>C and KLK3 À252A>G), previously reported to be associated with prostate cancer risk, were selected for large-scale analysis in 1,891 Finnish men (9,13). In addition, based on previous reports of positive association with prostate cancer, variants AR R726L and LHB I15T were included in the study (14,15).…”

Predictive and prognostic markers for invasive breast cancer

“…We identified two polymorphisms in the proximal promoter region of the PSA gene. These polymorphisms are located at positions − 252 (G or A) and − 205 (A or AA), and generate three genotypes 62,63 . The genotypes were associated with PSA mRNA expression.…”