SMUG1和NEIL2基因3' utr的遗传变异调节乳腺癌的风险、生存和治疗反应。

IF 2.5 4区 医学 Q3 GENETICS & HEREDITY
Mutagenesis Pub Date : 2021-08-27 DOI:10.1093/mutage/geab017
Andrea Cumova, Veronika Vymetalkova, Alena Opattova, Veronika Bouskova, Barbara Pardini, Katerina Kopeckova, Renata Kozevnikovova, Katerina Lickova, Miloslav Ambrus, Ludmila Vodickova, Alessio Naccarati, Pavel Soucek, Pavel Vodicka
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引用次数: 4

摘要

乳腺癌(BC)是女性中最常见的恶性肿瘤,全球每年约有200万新病例。已知一些遗传、表观遗传和环境因素参与了BC的发生和进展,包括由microRNAs (miRNAs)介导的转录后基因调控的改变。位于靶基因3'-非翻译区miRNA结合位点(mirsnp)的单核苷酸多态性(snp)可能影响miRNA结合亲和力,从而调节基因表达。我们之前报道过SMUG1和NEIL2基因中的mirsnp与结直肠癌患者的总生存期有显著关联。SMUG1和NEIL2是参与碱基切除DNA修复的DNA糖基酶。假设某些遗传特征在实体肿瘤中是常见的,我们在673例BC患者和675例健康女性对照中研究了SMUG1和NEIL2基因的变异是否与BC风险、预后和治疗反应相关。仅接受激素治疗的TC基因型NEIL2 rs6997097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)明显缩短。我们的研究结果表明,miRNAs操作的碱基切除修复糖基酶的调节可能会调节激素治疗的BC的预后。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response.

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.

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来源期刊
Mutagenesis
Mutagenesis 生物-毒理学
CiteScore
5.90
自引率
3.70%
发文量
22
审稿时长
6-12 weeks
期刊介绍: Mutagenesis is an international multi-disciplinary journal designed to bring together research aimed at the identification, characterization and elucidation of the mechanisms of action of physical, chemical and biological agents capable of producing genetic change in living organisms and the study of the consequences of such changes.
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