Department of Cell and Molecular Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran.
Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
BMC Med Genet. 2020 Apr 15;21(1):81. doi: 10.1186/s12881-020-01014-0.
Prostate cancer is one of the five common cancers and has the second incidence rate and the third mortality rate in Iranian population. The purpose of this study was to evaluate the association of rs16901979, rs4242382 and rs1447295 on 8q24 locus, rs2735839 (KLK3 gene) and rs721048 (EHBP1 gene) with prostate adenocarcinoma through multi-stage approach to identify the polymorphisms associated with prostate cancer and use them as screening factors. Screening tests can identify people who may have a chance of developing the disease before detection and any symptoms.
The case-control study included 103 cases (prostate adenocarcinoma) and 100 controls (benign prostatic hyperplasia). Tetra-primer ARMS-PCR was used to genotyping of each participant. A Multi-stage approach was used for efficient genomic study. In this method, a smaller number of people can be used. Chi-squared, Fisher's exact test and logistic regression were used to investigate the SNPs associated with prostate cancer and Gleason score.
In the first stage (59 men), the frequency of polymorphisms rs16901979, rs4242382, rs1447295, rs2735839 and rs721048 in the prostate adenocarcinoma group was evaluated compared to the control group (P-value < 0.3) in order to select meaningful polymorphisms. There was not any significant difference between genotype frequency rs16901979 (P = 0.671) and rs721048 (P = 0.474) in the case group compared to BPH. Therefore, these polymorphisms were eliminated, and in the second step (144 men), rs4242382, rs2735839 and rs1447295 were evaluated (P-value < 0.05). According to the total population (203 men), there was significant difference between genotype frequency rs4242382 (P = 0.001), rs2735839 (P = 0.000) and rs1447295 (P = 0.005) even after using Bonferroni correction (p = 0.016). The effect of these three polymorphisms on prostate cancer was not modified by age and PSA. There was a significant difference between the allelic frequency of A vs G (rs4242382, rs2735839) at all classes of Gleason score and A vs C (rs1447295) at Gleason score ≥ 8.
The results of this study for rs2735839, rs4242382 and rs1447295 indicate the association of these polymorphisms with prostate adenocarcinoma predisposition in Iranian population. Exposure effect is homogeneous between different ages and PSA level categories. These three polymorphisms should be studied in a larger population to confirm these results.
前列腺癌是五种常见癌症之一，在伊朗人群中发病率居第二位，死亡率居第三位。本研究旨在通过多阶段方法评估 rs16901979、rs4242382 和 rs1447295 位于 8q24 基因座、rs2735839（KLK3 基因）和 rs721048（EHBP1 基因）与前列腺腺癌的相关性，确定与前列腺癌相关的多态性，并将其作为筛查因子。筛查试验可以在检测和任何症状出现之前，识别出可能患有疾病的人群。
这项病例对照研究纳入了 103 例（前列腺腺癌）和 100 例（良性前列腺增生）患者。采用四引物 ARMS-PCR 对每位参与者进行基因分型。采用多阶段方法进行有效的基因组研究。在这种方法中，可以使用较少的人数。采用卡方检验、Fisher 确切检验和 logistic 回归分析与前列腺癌和 Gleason 评分相关的 SNP。
在第一阶段（59 名男性），与对照组相比，评估了前列腺腺癌组中 rs16901979、rs4242382、rs1447295、rs2735839 和 rs721048 多态性的频率（P 值<0.3），以选择有意义的多态性。与 BPH 相比，rs16901979（P=0.671）和 rs721048（P=0.474）的基因型频率之间没有显著差异。因此，这些多态性被排除在外，在第二步（144 名男性）中，评估了 rs4242382、rs2735839 和 rs1447295（P 值<0.05）。根据总人群（203 名男性），rs4242382（P=0.001）、rs2735839（P=0.000）和 rs1447295（P=0.005）的基因型频率存在显著差异，即使在使用 Bonferroni 校正后（P=0.016）。这三种多态性对前列腺癌的影响不受年龄和 PSA 的影响。在所有 Gleason 评分等级中，A 对 G（rs4242382、rs2735839）和 A 对 C（rs1447295）在 Gleason 评分≥8 时等位基因频率存在显著差异。
本研究中 rs2735839、rs4242382 和 rs1447295 的结果表明，这些多态性与伊朗人群中前列腺腺癌易感性相关。不同年龄和 PSA 水平类别之间的暴露效应是同质的。应在更大的人群中研究这三种多态性，以证实这些结果。
