Breast cancer (BC) is the most frequent malignancy in women accounting for approximately 2 million new cases worldwide annually. Several genetic, epigenetic and environmental factors are known to be involved in BC development and progression, including alterations in post-transcriptional gene regulation mediated by microRNAs (miRNAs). Single nucleotide polymorphisms (SNPs) located in miRNA binding sites (miRSNPs) in 3′-untranslated regions of target genes may affect miRNA-binding affinity and consequently modulate gene expression. We have previously reported a significant association of miRSNPs in the SMUG1 and NEIL2 genes with overall survival in colorectal cancer patients. SMUG1 and NEIL2 are DNA glycosylases involved in base excision DNA repair. Assuming that certain genetic traits are common for solid tumours, we have investigated wherever variations in SMUG1 and NEIL2 genes display an association with BC risk, prognosis, and therapy response in a group of 673 BC patients and 675 healthy female controls. Patients with TC genotype of NEIL2 rs6997097 and receiving only hormonal therapy displayed markedly shorter overall survival (HR = 4.15, 95% CI = 1.7–10.16, P = 0.002) and disease-free survival (HR = 2.56, 95% CI = 1.5–5.7, P = 0.02). Our results suggest that regulation of base excision repair glycosylases operated by miRNAs may modulate the prognosis of hormonally treated BC.

中文翻译：

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SMUG1 和 NEIL2 基因 3'UTR 的遗传变异调节乳腺癌风险、生存和治疗反应

乳腺癌 (BC) 是女性最常见的恶性肿瘤，每年在全球约有 200 万例新病例。已知几种遗传、表观遗传和环境因素参与 BC 的发展和进展，包括由 microRNA (miRNA) 介导的转录后基因调控的改变。位于靶基因 3'-非翻译区的 miRNA 结合位点 (miRSNP) 的单核苷酸多态性 (SNP) 可能会影响 miRNA 结合亲和力并因此调节基因表达。我们之前曾报道过 SMUG1 和 NEIL2 基因中的 miRNSNPs 与结直肠癌患者的总生存期显着相关。SMUG1 和 NEIL2 是参与碱基切除 DNA 修复的 DNA 糖基化酶。假设某些遗传特征对于实体瘤很常见，我们在 673 名 BC 患者和 675 名健康女性对照中调查了 SMUG1 和 NEIL2 基因变异与 BC 风险、预后和治疗反应相关的地方。具有 NEIL2 rs6997097 TC 基因型且仅接受激素治疗的患者的总生存期（HR = 4.15, 95% CI = 1.7–10.16, P = 0.002）和无病生存期（HR = 2.56, 95% CI = 1.5– 5.7，P = 0.02）。我们的研究结果表明，由 miRNA 操作的碱基切除修复糖基化酶的调节可能会调节激素治疗的 BC 的预后。具有 NEIL2 rs6997097 TC 基因型且仅接受激素治疗的患者的总生存期（HR = 4.15, 95% CI = 1.7–10.16, P = 0.002）和无病生存期（HR = 2.56, 95% CI = 1.5– 5.7，P = 0.02）。我们的研究结果表明，由 miRNA 操作的碱基切除修复糖基化酶的调节可能会调节激素治疗的 BC 的预后。具有 NEIL2 rs6997097 TC 基因型且仅接受激素治疗的患者的总生存期（HR = 4.15, 95% CI = 1.7–10.16, P = 0.002）和无病生存期（HR = 2.56, 95% CI = 1.5– 5.7，P = 0.02）。我们的研究结果表明，由 miRNA 操作的碱基切除修复糖基化酶的调节可能会调节激素治疗的 BC 的预后。