Linked Life Data

20177422

Source:http://linkedlifedata.com/resource/pubmed/id/20177422

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2010-9-24
pubmed:abstractText
There is increasing evidence that the Let-7 microRNA (miRNA) exerts an effect as a tumor suppressor by targeting the KRAS mRNA. The Let-7 complementary site (LCS6) T>G variant in the KRAS 3'-untranslated region weakens Let-7 binding. We analyzed whether the LCS6 variant may be clinically relevant to patients with metastatic colorectal cancer (MCRC) treated with anti-epidermal growth factor receptor (EGFR) therapy. LCS6 genotypes and KRAS/BRAF mutations were determined in the tumor DNA of 134 patients with MCRC who underwent salvage cetuximab-irinotecan therapy. There were 34 G-allele (T/G+G/G) carriers (25%) and 100 T/T genotype carriers (75%). G-allele carriers were significantly more frequent in the KRAS mutation group than in patients with KRAS wild type (P=0.004). In the 121 patients without BRAF V600E mutation, overall survival (OS) and progression-free survival (PFS) times were compared between carriers of the LCS6 G-allele genotypes and carriers of the wild-type T/T genotype. LCS6 G-allele carriers showed worse OS (P=0.001) and PFS (P=0.004) than T/T genotype carriers (confirmed in the multivariate model including the KRAS status). In the exploratory analysis of the 55 unresponsive patients with KRAS mutation, LCS6 G-allele carriers showed adverse OS and PFS times. These findings deserve additional investigations as they may open novel perspectives for the treatment of patients with MCRC.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1473-1150
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
458-64
pubmed:meshHeading
pubmed-meshheading:20177422-3' Untranslated Regions, pubmed-meshheading:20177422-Adult, pubmed-meshheading:20177422-Aged, pubmed-meshheading:20177422-Antibodies, Monoclonal, pubmed-meshheading:20177422-Antineoplastic Combined Chemotherapy Protocols, pubmed-meshheading:20177422-Camptothecin, pubmed-meshheading:20177422-Cohort Studies, pubmed-meshheading:20177422-Colorectal Neoplasms, pubmed-meshheading:20177422-Disease-Free Survival, pubmed-meshheading:20177422-Female, pubmed-meshheading:20177422-Genotype, pubmed-meshheading:20177422-Humans, pubmed-meshheading:20177422-Male, pubmed-meshheading:20177422-MicroRNAs, pubmed-meshheading:20177422-Middle Aged, pubmed-meshheading:20177422-Neoplasm Metastasis, pubmed-meshheading:20177422-Proto-Oncogene Proteins, pubmed-meshheading:20177422-Retrospective Studies, pubmed-meshheading:20177422-Salvage Therapy, pubmed-meshheading:20177422-ras Proteins
pubmed:year
2010
pubmed:articleTitle
Genetic modulation of the Let-7 microRNA binding to KRAS 3'-untranslated region and survival of metastatic colorectal cancer patients treated with salvage cetuximab-irinotecan.
pubmed:affiliation
Department of Onco-Hematology, Medical Oncology Unit, Azienda Ospedaliera Ospedale San Salvatore, Pesaro, Italy. frada@tin.it
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, Non-U.S. Gov't