Association of Short Tandem Repeat Polymorphism in the Promoter of Prostate Cancer Antigen 3 Gene with the Risk of Prostate Cancer

Abstract

Background PCA3 (prostate cancer antigen 3) gene is one of the most prostate cancer-specific genes at present. Consequently, the prostate-specific expression and the sharp up-regulation of PCA3 mRNA in prostate cancer suggest a unique transcriptional regulation, which possibly can be attributed to promoter polymorphism. In our study, we evaluated whether there is polymorphism in PCA3 promoter region and also assess the association of the polymorphism with prostate cancer.Methodology/Principal FindingsWe designed a specific primer set to screen the promoter of PCA3 gene by polymerase chain reaction (PCR)-based cloning and sequencing with the DNA extracted from peripheral blood samples of prostate cancer (PCa) cases (n = 186) and healthy control cases (n = 135). Genotype-specific risks were estimated as odds ratios (ORs) with associated 95% confidence intervals (CIs) by chi-square test. Possible deviation of the genotype frequencies from controls and PCa cases expected under Hardy-Weinberg equilibrium was assessed by the chi-square test. Short tandem repeat polymorphism of TAAA was found in the promoter region of PCA3 gene, five polymorphisms and eight genotypes were identified. The eight genotypes were divided into three groups: ≤10TAAA, 11TAAA, ≥12TAAA. The group 11TAAA and ≥12TAAA were associated with higher relative risk for prostate cancer than group ≤10TAAA (OR = 1.76, 95%CI = 1.07–2.89[for group 11TAAA]; OR = 5.28, 95%CI = 1.76–15.89[for group ≥12TAAA]).Conclusions/SignificanceThe presence of the (TAAA)n short tandem repeat polymorphisms in the PCA3 promoter region may be a risk factor for prostate cancer in the Chinese population.

Long noncoding RNA PCA3 gene promoter region is related to the risk of prostate cancer on Chinese males

“…Short tandem repeat polymorphism of TAAA was found in the promoter region of PCA3 gene. We demonstrated a significant association between the presence of the (TAAA)n STR polymorphisms in the PCA3 promoter region and PCa in Chinese populations (Zhou et al, 2011). These findings indicate that the PCA3 promoter STR is a genetic susceptibility factor for PCa.…”

“…Each repeat number was calculated of these cloned alleles used as size markers. So corresponded to total numbers of TAAA repeat in the alleles, eight genotypes were classified into three groups: ≤ 10TAAA, 11TAAA, and ≥ 12TAAA (Zhou et al, 2011) (e.g. the total TAAA repeat numbers of genotype (TAAA)n/(TAAA)m is x [x = n + m],which will be put into the "x" TAAA group).…”

Polymorphisms in MMP-2 and TIMP-2 in Turkish patients with prostate cancer

“…Among them, prostate cancer is the second most frequent cancer type after lung cancer and the sixth leading cause of death, accounting for 14% (903,500) of new cases and 6% (258,400) of deaths in males in 2008 (1). Prostate cancer, a multifactorial disease, is the most commonly diagnosed malignancy, and the early diagnosis of prostate cancer is very important due to its increasing incidence worldwide (2).…”

Factors modifying transcriptional regulation of signaling genes have putative role in tumor development and progression in humans

“…The eight genotypes were divided into three groups: 610TAAA, 11TAAA, P12TAAA. The group 11TAAA and P12TAAA were associated with higher relative risk for prostate cancer than group 610TAAA (OR = 1.76, 95% CI = 1.07-2.89 [for group 11TAAA]; OR = 5.28, 95% CI = 1.76-15.89 [for group P12TAAA]) [4].…”

“…One polymorphism in coding region substitutes Ile 105 Val in the substrate-binding site of GSTP1 and thus reduces the catalytic activity of enzyme [3]. More recently copy number variation and short tandem repeat polymorphisms and their role in gene regulation and cancer development have been explored [4][5][6]. Moreover, polymorphisms may also play roles in evolution and drug response to a particular drug.…”