Study On The Correlation Of Androgen Receptor Gene (CAG)_n Repeat Polymorphisms With The Risk Of Prostate Cancer

Section1Association between androgen receptor gene (CAG)n repeat polymorphisms and the risk of prostate cancer among northern Chinese men:A case-control studyObjectives To derive an association between androgen receptor (AR) gene (CAG) n repeat polymorphisms and prostate cancer (PCa) risk among northern Chinese men.Materials and methods140PCa patients and206age-matched healthy men were analysed retrospectively.Clinical records of the subjects were collected and genomic DNA was extracted from peripheral blood leucocytes employing the salting-out DNA isolation method. The first exon of the AR gene was amplified by PCR and the primer was fluorescently labeled with FAM. Genotyping of the (CAG) n repeat polymorphisms was performed using capillary electrophoresis and the results were verified by Sanger sequencing method. The exact (CAG) n repeat number was estimated by genotyping results. The genotype frequencies for the AR gene (CAG) n repeat between PCa group and control group was compared. The association between (CAG) n repeat polymorphisms and age, BMI, PSA, Gleason score, tumor stage of PCa patients were also evaluated. Means between PCa group and control group were compared using Student’s t-test or Mann-Whitney U test. Pearson chi-square test was used to compare genotype frequencies between the two groups. The odd ratios (OR) corresponding to95%confidence interval (95%CI) were calculated. A P value<0.05was considered statistically significant. Statistical analysis was carried out using the SPSS19.0computer package.Result A total of323subjects with full data were included in the final analysis,126in the PCa group and197in the control group. There was no significant difference of age and BMI between PCa group and control group (P>0.05). The mean number of AR gene (CAG) n repeats in the PCa group was significantly shorter than in the control group, which were19.81±3.30and20.58±2.75respectively (P<0.05). Compared with control group, the frequence of short (CAG) n repeat (<20) AR gene was significantly higher in the PCa group (OR=1.70,95%CI:1.06,2.71, P<0.05). Short (CAG)n repeat was also a risk factor of high grade (Gleason score>7) tumor (OR=4.12,95%CI:1.84,9.23, P<0.01). However, no significant associations were detected between the AR gene (CAG) n repeat polymorphisms and age, BMI, PSA and tumor stage within PCa group (P>0.05). Conclusions The AR gene (CAG) n repeat polymorphisms were correlated with PCa risk among northern Chinese men. Short (CAG) n repeat (<20) may contribute to PCa susceptibility and high grade tumor. Section2Correlation of androgen receptor gene (CAG)n repeat polymorphisms with the risk of prostate cancer among multi-population:A Meta-analysisObjectives To access the correlation between androgen receptor (AR) gene (CAG) n repeat polymorphisms and prostate cancer (PCa) risk among multi-population using meta-analysis method.Materials and methods Journal articles on the association between AR gene (CAG) n repeats and PCa risk were identified from database published up to August2013. Articles were selected with inclusion/exclusion criteria, and the study of section one was added for meta-analysis. Information from all available studies was extracted blindly and independently by two authors. Stata version12.0was used for the meta-analysis. Q statistic wad performed and subgroup analysis was conducted to expore the source of heterogeneity. Effect size was pooled using Mantel-Haenszel fixed-effect model or random-effects model, and the risk of PCa was assessed by calculating the pooled odd ratio (OR) and the95%confidence interval (95%CI). Ethnicity was stratified for the subgroup analysis. Sensitivity and cumulative analysis were conducted to evaluate the quality and consistency of the results. The potential publication bias was measured using the Begg’s test and Egger’s test and funnel plot were performed. If publication bias existed, the non-parametric’trim and fill’method was used to adjust for it.Results31of215studies and our study were included in this meta-analysis. Caucasians, Asians, Africans and Hispanics were included in the study population. In total, there were5,516PCa patients and6,834healthy controls. Heterogeneity was observed (I2=76.2%, P<0.05) among studies and was greater within Asians (I2=81.5%) and Africans (I2=88.0%). Pooled effects were estimated by using the random-effects model. Short (CAG) n repeat AR gene significantly increase the risk of PCa (OR=1.61,95%CI:1.34,1.94). Subgroup analysis showed that the contribution of shorter (CAG) n repeat on the susceptibility of PCa was predominant in Caucasians (OR=1.37,95%CI:1.15,1.63) and Asians (OR=2.10,95%CI:1.38,3.19). No significant correlations between (CAG) n repeat and PCa risk in Africans and Hispanics were detected. The result of meta-analysis was proved stable and robust through both sensitivity and cumulative analysis. Although significant publication bias was observed by Begg’s and Egger’s test (P<0.05), there was no significant difference for pooled ORs before and after using’trim and fill’method. Conclusions Ethnicity plays an important role on the correlation between the AR gene (CAG) n repeat polymorphisms and PCa risk. Short (CAG) n repeat may increase the PCa risk in Caucasians and Asians but not in Africans and Hispanics.