Department of Biology, University of Guilan, Rasht, Iran.
Cellular and Molecular Research Center, Faculty of Medicine, Guilan University of Medical Sciences, Rasht, Iran.
Gene. 2019 Sep 5;712:143954. doi: 10.1016/j.gene.2019.143954. Epub 2019 Jul 6.
Breast cancer (BC) is the highest cause of mortality among female cancer patients. In some cases, BC is due to Poly [ADP-ribose] polymerase 1 (PARP1) gene dysregulation, which has been involved in various important cellular processes. Among Iranian women, the association between PARP1 polymorphisms and BC was never studied before so in this case-control study, the genetic association of three SNPs (rs1136410, rs907187 and rs4653734) was analyzed with susceptibility to BC.
The study subjects were 386 Iranian females divided into 186 patients and 200 healthy controls. The genotypes of PARP1 variants were detected using ARMS and a combined ARMS-RFLP PCR method.
The results showed that Carriers of CG and GG genotypes of the variant rs4653734 were at higher risk of BC compared with wild-type carriers (CC) and this variant was statistically significant under a recessive model of inheritance. Moreover, rs907187 was related to increased BC risk in the CC and GG genotypes under dominant and recessive models of inheritance. The G allele frequency of rs4653734 and rs907187 was higher in breast cancer patients than in normal subjects. No association was detected between rs1136410 and susceptibility to BC among studied groups. Furthermore, A-G-C haplotype was linked to an increased BC risk, whereas A-C-C and A-C-G haplotypes were related to a decreased risk of BC. In Silico predictions suggested that rs907187 affects E2F and E2F-4 transcription factors binding site.
The current study suggests that rs907187 and rs4653734 have remarkable associations with BC risk among Iranian women.
乳腺癌（BC）是女性癌症患者死亡的主要原因。在某些情况下，BC 是由于聚 [ADP-核糖] 聚合酶 1（PARP1）基因失调引起的，该基因参与了各种重要的细胞过程。在伊朗女性中，PARP1 多态性与 BC 的关联从未被研究过，因此在这项病例对照研究中，分析了三个 SNP（rs1136410、rs907187 和 rs4653734）的遗传关联与 BC 的易感性。
研究对象为 386 名伊朗女性，分为 186 名患者和 200 名健康对照。使用 ARMS 和联合 ARMS-RFLP PCR 方法检测 PARP1 变体的基因型。
结果表明，与野生型携带者（CC）相比，变体 rs4653734 的 CG 和 GG 基因型携带者患乳腺癌的风险更高，这种变体在隐性遗传模型下具有统计学意义。此外，rs907187 在 CC 和 GG 基因型的显性和隐性遗传模型下与增加的 BC 风险相关。rs4653734 和 rs907187 的 G 等位基因频率在乳腺癌患者中高于正常人群。在所研究的组中，未发现 rs1136410 与 BC 的易感性相关。此外，A-G-C 单倍型与增加的 BC 风险相关，而 A-C-C 和 A-C-G 单倍型与降低的 BC 风险相关。In Silico 预测表明 rs907187 影响 E2F 和 E2F-4 转录因子结合位点。
本研究表明，rs907187 和 rs4653734 与伊朗女性的 BC 风险显著相关。
