RGD Reference Report - Double-strand break repair and colorectal cancer: gene variants within 3' UTRs and microRNAs binding as modulators of cancer risk and clinical outcome. - Rat Genome Database

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Double-strand break repair and colorectal cancer: gene variants within 3' UTRs and microRNAs binding as modulators of cancer risk and clinical outcome.

Authors: Naccarati, Alessio  Rosa, Fabio  Vymetalkova, Veronika  Barone, Elisa  Jiraskova, Katerina  Di Gaetano, Cornelia  Novotny, Jan  Levy, Miroslav  Vodickova, Ludmila  Gemignani, Federica  Buchler, Tomas  Landi, Stefano  Vodicka, Pavel  Pardini, Barbara 
Citation: Naccarati A, etal., Oncotarget. 2016 Apr 26;7(17):23156-69. doi: 10.18632/oncotarget.6804.
RGD ID: 151361212
Pubmed: PMID:26735576   (View Abstract at PubMed)
PMCID: PMC5029617   (View Article at PubMed Central)
DOI: DOI:10.18632/oncotarget.6804   (Journal Full-text)

Genetic variations in 3' untranslated regions of target genes may affect microRNA binding, resulting in differential protein expression. microRNAs regulate DNA repair, and single-nucleotide polymorphisms in miRNA binding sites (miRSNPs) may account for interindividual differences in the DNA repair capacity. Our hypothesis is that miRSNPs in relevant DNA repair genes may ultimately affect cancer susceptibility and impact prognosis.In the present study, we analysed the association of polymorphisms in predicted microRNA target sites of double-strand breaks (DSBs) repair genes with colorectal cancer (CRC) risk and clinical outcome. Twenty-one miRSNPs in non-homologous end-joining and homologous recombination pathways were assessed in 1111 cases and 1469 controls. The variant CC genotype of rs2155209 in MRE11A was strongly associated with decreased cancer risk when compared with the other genotypes (OR 0.54, 95% CI 0.38-0.76, p = 0.0004). A reduced expression of the reporter gene was observed for the C allele of this polymorphism by in vitro assay, suggesting a more efficient interaction with potentially binding miRNAs. In colon cancer patients, the rs2155209 CC genotype was associated with shorter survival while the TT genotype of RAD52 rs11226 with longer survival when both compared with their respective more frequent genotypes (HR 1.63, 95% CI 1.06-2.51, p = 0.03 HR 0.60, 95% CI 0.41-0.89, p = 0.01, respectively).miRSNPs in DSB repair genes involved in the maintenance of genomic stability may have a role on CRC susceptibility and clinical outcome.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
MRE11Humancolon cancer susceptibilityIAGP DNA:SNP:3'utr: (rs2155209) (human)RGD 
Mre11Ratcolon cancer susceptibilityISOMRE11 (Homo sapiens)DNA:SNP:3'utr: (rs2155209) (human)RGD 
Mre11aMousecolon cancer susceptibilityISOMRE11 (Homo sapiens)DNA:SNP:3'utr: (rs2155209) (human)RGD 
RAD52Humancolon cancer susceptibilityIAGP DNA:SNPs:3'utr: (rs1051669 and rs11571475) (human)RGD 
Rad52Ratcolon cancer susceptibilityISORAD52 (Homo sapiens)DNA:SNPs:3'utr: (rs1051669 and rs11571475) (human)RGD 
Rad52Mousecolon cancer susceptibilityISORAD52 (Homo sapiens)DNA:SNPs:3'utr: (rs1051669 and rs11571475) (human)RGD 
RAD52Humancolorectal cancer susceptibilityIAGP DNA:SNPs:3'utr: (rs7963551 and rs11226) (human)RGD 
Rad52Mousecolorectal cancer susceptibilityISORAD52 (Homo sapiens)DNA:SNPs:3'utr: (rs7963551 and rs11226) (human)RGD 
Rad52Ratcolorectal cancer susceptibilityISORAD52 (Homo sapiens)DNA:SNPs:3'utr: (rs7963551 and rs11226) (human)RGD 
MRE11Humanrectum cancer susceptibilityIAGP DNA:SNP:3'utr: (rs2155209) (human)RGD 
Mre11Ratrectum cancer susceptibilityISOMRE11 (Homo sapiens)DNA:SNP:3'utr: (rs2155209) (human)RGD 
Mre11aMouserectum cancer susceptibilityISOMRE11 (Homo sapiens)DNA:SNP:3'utr: (rs2155209) (human)RGD 
NBNHumanrectum cancer susceptibilityIAGP DNA:SNP:3'utr: (rs14448) (human)RGD 
NbnRatrectum cancer susceptibilityISONBN (Homo sapiens)DNA:SNP:3'utr: (rs14448) (human)RGD 
NbnMouserectum cancer susceptibilityISONBN (Homo sapiens)DNA:SNP:3'utr: (rs14448) (human)RGD 
XRCC5Humanrectum cancer susceptibilityIAGP DNA:SNP:3'utr: (rs1051677) (human)RGD 
Xrcc5Ratrectum cancer susceptibilityISOXRCC5 (Homo sapiens)DNA:SNP:3'utr: (rs1051677) (human)RGD 
Xrcc5Mouserectum cancer susceptibilityISOXRCC5 (Homo sapiens)DNA:SNP:3'utr: (rs1051677) (human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
RAD52HumanColon cancer susceptibilityIAGP DNA:SNPs:3'utr: (rs1051669 and rs11571475) (human)RGD 
RAD52HumanNeoplasm of the large intestine susceptibilityIAGP DNA:SNPs:3'utr: (rs7963551 and rs11226) (human)RGD 
MRE11HumanNeoplasm of the rectum susceptibilityIAGP DNA:SNP:3'utr: (rs2155209) (human)RGD 
NBNHumanNeoplasm of the rectum susceptibilityIAGP DNA:SNP:3'utr: (rs14448) (human)RGD 
XRCC5HumanNeoplasm of the rectum susceptibilityIAGP DNA:SNP:3'utr: (rs1051677) (human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Mre11  (MRE11 homolog, double strand break repair nuclease)
Nbn  (nibrin)
Rad52  (RAD52 homolog, DNA repair protein)
Xrcc5  (X-ray repair cross complementing 5)

Genes (Mus musculus)
Mre11a  (MRE11A homolog A, double strand break repair nuclease)
Nbn  (nibrin)
Rad52  (RAD52 homolog, DNA repair protein)
Xrcc5  (X-ray repair complementing defective repair in Chinese hamster cells 5)

Genes (Homo sapiens)
MRE11  (MRE11 homolog, double strand break repair nuclease)
NBN  (nibrin)
RAD52  (RAD52 homolog, DNA repair protein)
XRCC5  (X-ray repair cross complementing 5)


Additional Information