Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Department of Biochemistry, Institute of Home Economics, University of Delhi, New Delhi, India.
Gene. 2019 Jan 15;682:25-32. doi: 10.1016/j.gene.2018.10.010. Epub 2018 Oct 6.
Different diseases have been associated with PARK2/PACRG overlapping promoter polymorphisms (rs2276201 and rs9347683) in the recent past. However association of these polymorphisms with cancer remains elusive till date. Thus in this study we evaluated association between these polymorphisms and colorectal cancer (CRC) incidences among North Indians. Genomic DNA was isolated using venous blood of 400 unrelated subjects (200 CRC cases and 200 healthy controls) of North Indian origin. Both SNPs were genotyped using PCR-RFLP method. Promoter methylation status in tumor DNA was checked using MS-PCR. Statistical analysis was performed using SPSS-17 software. In-silico predictions for transcription factor binding were performed using "PROMO" a freely available online tool. SNP rs2276201 showed statistically significant difference (P = 0.047) among cases and controls while rs9347683 did not (P = 0.113). The TC genotype (OR: 1.855, 95% CI: 1.021-3.369, P = 0.043), CC genotype (OR: 1.617, 95% CI: 1.042-2.510, P = 0.032), TT vs CT+CC genetic model (OR: 1.60, P = 0.0158) and allelic model (OR: 1.3931, 95% CI: 1.0498-1.8485, P = 0.0214) of rs2276201 showed significant risk for CRC. For rs9347683 AC genotype (OR: 1.604, 95% CI: 1.019-2.523, P = 0.041) and AA vs AC+CC genetic model (OR: 1.57, P = 0.039) showed significant risk. Haplotype CC provided significant risk (OR: 1.618, 95% CI: 1.112-2.352, P = 0.011) whereas haplotype TA provided significant protection (OR: 0.732, 95% CI: 0.543-0.987, P = 0.040) against CRC. Promoter methylation was significantly higher in tumor grade III + IV (OR: 2.37, P = 0.019), while PARK2 expression was lower in cancer tissues compared to normal tissue. Here we provide the first report where PARK2 promoter SNP's rs2276201 and rs9347683 are shown to be significantly associated with the risk of CRC development.
不同的疾病与 PARK2/PACRG 重叠启动子多态性（rs2276201 和 rs9347683）有关。然而，这些多态性与癌症的关联至今仍不清楚。因此，在这项研究中，我们评估了这些多态性与北印度人结直肠癌（CRC）发病率之间的关系。使用静脉血从 400 名无亲缘关系的受试者（200 名 CRC 病例和 200 名健康对照）中分离基因组 DNA。使用 PCR-RFLP 方法对这两种 SNP 进行基因分型。使用 MS-PCR 检查肿瘤 DNA 中的启动子甲基化状态。使用 SPSS-17 软件进行统计分析。使用“PROMO”免费在线工具进行转录因子结合的计算机预测。SNP rs2276201 在病例和对照组之间显示出统计学显著差异（P=0.047），而 rs9347683 则没有（P=0.113）。TC 基因型（OR：1.855，95%CI：1.021-3.369，P=0.043）、CC 基因型（OR：1.617，95%CI：1.042-2.510，P=0.032）、TT 与 CT+CC 遗传模型（OR：1.60，P=0.0158）和等位基因模型（OR：1.3931，95%CI：1.0498-1.8485，P=0.0214）的 rs2276201 显示出对 CRC 的显著风险。rs9347683 的 AC 基因型（OR：1.604，95%CI：1.019-2.523，P=0.041）和 AA 与 AC+CC 遗传模型（OR：1.57，P=0.039）显示出显著风险。CC 单倍型提供了显著的风险（OR：1.618，95%CI：1.112-2.352，P=0.011），而 TA 单倍型提供了显著的保护（OR：0.732，95%CI：0.543-0.987，P=0.040），可以降低 CRC 的发病风险。肿瘤分级 III+IV 中启动子甲基化显著升高（OR：2.37，P=0.019），而癌症组织中的 PARK2 表达低于正常组织。在这里，我们首次报道了 PARK2 启动子 SNP rs2276201 和 rs9347683 与 CRC 发病风险显著相关。
