Department of Toxicology and Carcinogenesis, Nofer Institute of Occupational Medicine, Lodz, Poland.
Department of Molecular Genetics and Epigenetics, Nofer Institute of Occupational Medicine, Lodz, Poland.
PLoS One. 2020 Jan 6;15(1):e0226976. doi: 10.1371/journal.pone.0226976. eCollection 2020.
A case-control study was conducted in which we evaluated the association between genetic variability of DNA repair proteins belonging to the Rad51 family and breast cancer (BrC) risk. In the study, 132 female BrC cases and 189 healthy control females were genotyped for a total of 14 common single nucleotide polymorphisms (SNPs) within Rad51 and Xrcc3. Moreover, our previously reported Rad51C genetic data were involved to explore the nonlinear interactions among SNPs within the three genes and effect of such interactions on BrC risk. The rare rs5030789 genotype (-4601AA) in Rad51 was found to significantly decrease the BrC risk (OR = 0.5, 95% CI: 0.3-1.0, p<0.05). An interaction between this SNP, rs2619679 and rs2928140 (both in Rad51), was found to result in a two three-locus genotypes -4719AA/-4601AA/2972CG and -4719AT/-4601GA/2972CC, both of which were found to increase the risk of BrC (OR = 8.4, 95% CI: 1.8-38.6, p<0.0001), instead. Furthermore, rare Rad51 rs1801320 (135CC) and heterozygous Xrcc3 rs3212057 (10343GA) genotypes were found to respectively increase (OR = 10.6, 95% CI: 1.9-198, p<0.02) and decrease (OR = 0.0, 95% CI: 0.0-NA, p<0.05) the risk of BrC. Associations between these SNPs and BrC risk were further supported by outcomes of employed machine learning analyses. In Xrcc3, the 4541A/9685A haplotype was found to be significantly associated with reduced BrC risk (OR = 0.5; 95% CI: 0.3-0.9; p<0.05). Concluding, our study indicates a complex role of SNPs within Rad51 (especially rs5030789) and Xrcc3 in BrC, although their significance with respect to the disease needs to be further clarified.
我们进行了一项病例对照研究，评估了属于 Rad51 家族的 DNA 修复蛋白的遗传变异性与乳腺癌（BrC）风险之间的关联。在这项研究中，我们对 132 名女性 BrC 病例和 189 名健康对照女性进行了基因分型，总共检测了 Rad51 和 Xrcc3 中 14 个常见的单核苷酸多态性（SNP）。此外，我们还涉及了先前报道的 Rad51C 遗传数据，以探讨这三个基因内 SNP 之间的非线性相互作用以及这种相互作用对 BrC 风险的影响。结果发现，Rad51 中的罕见 rs5030789 基因型（-4601AA）显著降低了 BrC 风险（OR=0.5，95%CI：0.3-1.0，p<0.05）。还发现，该 SNP（rs2619679 和 rs2928140，均位于 Rad51 中）与 rs2928140 之间存在相互作用，导致两种三个基因座基因型（-4719AA/-4601AA/2972CG 和 -4719AT/-4601GA/2972CC），这两种基因型都被发现增加了 BrC 的风险（OR=8.4，95%CI：1.8-38.6，p<0.0001）。此外，罕见的 Rad51 rs1801320（135CC）和杂合 Xrcc3 rs3212057（10343GA）基因型分别被发现增加（OR=10.6，95%CI：1.9-198，p<0.02）和降低（OR=0.0，95%CI：0.0-NA，p<0.05）BrC 的风险。这些 SNP 与 BrC 风险之间的关联也得到了所采用的机器学习分析结果的支持。在 Xrcc3 中，发现 4541A/9685A 单倍型与降低 BrC 风险显著相关（OR=0.5；95%CI：0.3-0.9；p<0.05）。总之，我们的研究表明，Rad51（特别是 rs5030789）和 Xrcc3 内的 SNP 与 BrC 之间存在复杂的作用，尽管它们与疾病的相关性需要进一步阐明。
