Genome Biology Laboratory, Department of Biosciences, Jamia Millia Islamia, New Delhi, India.
Department of Biochemistry, Institute of Home Economics, University of Delhi, Delhi, India.
J Gastrointest Cancer. 2022 Sep;53(3):674-682. doi: 10.1007/s12029-021-00693-z. Epub 2021 Aug 31.
PARK2 is a potential tumour suppressor gene and its genetic alterations (regionic loss) are common across many human cancers. The association of PARK2 germline variations (SNPs) with Parkinson's has been shown, but their association in development and progression of cancer remains elusive. The aim of this study was to identify association of PARK2 polymorphisms (rs1801474, rs1801334) with colorectal cancer in a case control study design.
This case control study included a total of 650 genetically unrelated subjects comprising 300 colorectal cancer cases and 350 healthy controls belonging to North Indian. Both SNPs were analyzed using the PCR-RFLP assay. Statistical analysis for describing risk and association was performed using SPSS-17 software. Structural deviations due to non- synonymous substitutions (S167N and D394N) were analyzed using MD simulations.
The genotype distributions of both the SNPs were in Hardy-Weinberg equilibrium. For both the polymorphisms, the allelic model showed statistically significant risk with OR ~ 1.3. Many of the associations remained significant even after Bonferroni correction (P < 0.00125). The result suggested that both S167N and D394N were deviated from wild type and structures and were stable after 5 ns. The average value of RMSD for backbone atoms was calculated from 5 to 10 ns molecular dynamics simulation data.
In conclusion, our study revealed a significant association of PARK2 SNPs with colorectal cancer as well as their relations with other clinical parameters highlighting their contribution towards colorectal cancer susceptibility in North Indian population.
PARK2 是一种潜在的肿瘤抑制基因，其遗传改变（区域缺失）在许多人类癌症中很常见。已经表明 PARK2 种系变异（SNP）与帕金森病有关，但它们在癌症的发展和进展中的关联仍不清楚。本研究的目的是在病例对照研究设计中确定 PARK2 多态性（rs1801474、rs1801334）与结直肠癌的关联。
本病例对照研究共纳入 650 名无遗传关系的受试者，包括 300 例结直肠癌病例和 350 例来自印度北部的健康对照者。采用 PCR-RFLP 检测法分析两个 SNP。使用 SPSS-17 软件进行描述风险和关联的统计分析。使用 MD 模拟分析由于非同义替换（S167N 和 D394N）引起的结构偏差。
两个 SNP 的基因型分布均符合 Hardy-Weinberg 平衡。对于这两种多态性，等位基因模型显示具有统计学意义的风险，OR 值约为 1.3。许多关联在经过 Bonferroni 校正后仍然显著（P < 0.00125）。结果表明，S167N 和 D394N 均偏离野生型结构，在 5 ns 后稳定。从 5 到 10 ns 分子动力学模拟数据计算了骨架原子的 RMSD 的平均值。
总之，我们的研究表明 PARK2 SNP 与结直肠癌显著相关，以及它们与其他临床参数的关系，突出了它们对印度北部人群结直肠癌易感性的贡献。
