Pavel Anca Gabriela, Stambouli Danae, Anton Gabriela, Gener Ismail, Preda Adrian, Baston Catalin, Gingu Constantin
Cytogenomic Medical Laboratory, Molecular Genetics Department, 014453 Bucharest, Romania.
The Romania Academy, "Stefan S. Nicolau" Institute of Virology, 030304 Bucharest, Romania.
Biomedicines. 2022 Oct 28;10(11):2733. doi: 10.3390/biomedicines10112733.
Single nucleotide polymorphisms (SNPs) are the most common type of genetic variation among people. Genome Wide Association studies (GWASs) have generated multiple genetic variants associated with prostate cancer (PC) risk. Taking into account previously identified genetic susceptibility variants, the purpose of our study was to determine the cumulative association between four common SNPs and the overall PC risk. A total of 78 specimens from both PC and benign prostate hyperplasia (BPH) patients were included in the study. Genotyping of all selected SNPs was performed using the TaqMan assay. The association between each SNP and the PC risk was assessed individually and collectively. Analysis of the association between individual SNPs and PC risk revealed that only the rs4054823 polymorphism was significantly associated with PC, and not with BPH (p < 0.001). Statistical analysis also showed that the heterozygous genotype of the rs2735839 polymorphism is more common within the BPH group than in the PC group (p = 0.042). The cumulative effect of high-risk alleles on PC was analyzed using a logistic regression model. As a result, the carriers of at least one risk allele copy in each particular region had a cumulative odd ratio (OR) of 1.42 times, compared to subjects who did not have any of these factors. In addition, the combination of these four genetic variants increased the overall risk of PC by 52%. Our study provides further evidence of the cumulative effects of genetic risk factors on overall PC risk. These results should encourage future research to explain the interactions between known susceptibility variants and their contribution to the development and progression of PC disease.
单核苷酸多态性（SNPs）是人群中最常见的遗传变异类型。全基因组关联研究（GWASs）已产生了多个与前列腺癌（PC）风险相关的遗传变异。考虑到先前已确定的遗传易感性变异，我们研究的目的是确定四个常见单核苷酸多态性与总体前列腺癌风险之间的累积关联。该研究共纳入了78例前列腺癌患者和良性前列腺增生（BPH）患者的标本。使用TaqMan分析对所有选定的单核苷酸多态性进行基因分型。分别和综合评估每个单核苷酸多态性与前列腺癌风险之间的关联。对单个单核苷酸多态性与前列腺癌风险之间关联的分析表明，只有rs4054823多态性与前列腺癌显著相关，而与良性前列腺增生无关（p < 0.001）。统计分析还表明，rs2735839多态性的杂合基因型在良性前列腺增生组中比在前列腺癌组中更常见（p = 0.042）。使用逻辑回归模型分析高危等位基因对前列腺癌的累积效应。结果显示，与没有任何这些因素的受试者相比，每个特定区域中至少携带一个风险等位基因拷贝的携带者的累积比值比（OR）为1.42倍。此外，这四种遗传变异的组合使前列腺癌的总体风险增加了52%。我们的研究进一步证明了遗传风险因素对总体前列腺癌风险的累积效应。这些结果应鼓励未来的研究来解释已知易感性变异之间的相互作用及其对前列腺癌疾病发生和发展的贡献。
