Genetic variations in 3'UTRs of SMUG1 and NEIL2 genes modulate breast cancer risk, survival and therapy response
Language English Country Great Britain, England Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
34097065
DOI
10.1093/mutage/geab017
PII: 6294167
Knihovny.cz E-resources
- MeSH
- 3' Untranslated Regions * MeSH
- White People genetics MeSH
- DNA Glycosylases genetics MeSH
- DNA-(Apurinic or Apyrimidinic Site) Lyase genetics MeSH
- Adult MeSH
- Polymorphism, Single Nucleotide * MeSH
- Middle Aged MeSH
- Humans MeSH
- MicroRNAs metabolism MeSH
- Breast Neoplasms enzymology epidemiology genetics therapy MeSH
- DNA Repair MeSH
- Disease-Free Survival MeSH
- Prognosis MeSH
- Risk MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Uracil-DNA Glycosidase genetics MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 3' Untranslated Regions * MeSH
- DNA Glycosylases MeSH
- DNA-(Apurinic or Apyrimidinic Site) Lyase MeSH
- MicroRNAs MeSH
- NEIL2 protein, human MeSH Browser
- SMUG1 protein, human MeSH Browser
- Uracil-DNA Glycosidase MeSH
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.
Biomedical Centre Faculty of Medicine in Pilsen Charles University Pilsen 306 05 Czech Republic
Candiolo Cancer Institute FPO IRCCS Candiolo 10060 Italy
IIGM Italian Institute for Genomic Medicine Candiolo 10060 Italy
Onkocentrum MEDICON Services s r o Prague 14000 Czech Republic
Toxicogenomics Unit National Institute of Public Health Prague 10000 Czech Republic
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