title: A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers.
abstract: MicroRNA (miRNA)-binding site polymorphisms that could contribute to disease risk and prognosis are rapidly being identified and investigated as this genetic variation may have a potentially profound impact on human health. A recently described variant allele in the KRAS 3' untranslated region that arises in the let-7 miRNA complementary site (KRAS-LCS6) and leads to increased KRAS expression in lung cancer was examined for its association with the occurrence of head and neck squamous cell carcinoma (HNSCC). We examined the prevalence of the KRAS-LCS6 variant allele in a population-based case-control study of HNSCC to determine if this KRAS-LCS6 genotype was associated with disease occurrence and patient survival. Although the KRAS-LCS6 variant genotype was not associated with the overall risk of HNSCC, cases with the KRAS-LCS6 variant genotype had significantly reduced survival [hazard ratio (HR), 1.6; 95% confidence interval (CI), 1.0-2.5] in models controlled for confounders of survival. This risk was greatest in cases of oral cavity carcinoma (HR, 2.7; 95% CI, 1.4-5.3). These data demonstrate that cases with the KRAS-LCS6 variant have significantly reduced survival time and suggest that this variant may alter the phenotype or therapeutic response of this disease.
authors.affiliation: Department of Pathology and Laboratory Medicine, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, USA.
authors.forename: Brock C
authors.initials: BC
authors.lastname: Christensen
authors.forename: Benjamin J
authors.initials: BJ
authors.lastname: Moyer
authors.forename: Michele
authors.initials: M
authors.lastname: Avissar
authors.forename: Lauren G
authors.initials: LG
authors.lastname: Ouellet
authors.forename: Silvia L
authors.initials: SL
authors.lastname: Plaza
authors.forename: Michael D
authors.initials: MD
authors.lastname: McClean
authors.forename: Carmen J
authors.initials: CJ
authors.lastname: Marsit
authors.forename: Karl T
authors.initials: KT
authors.lastname: Kelsey
mesh_terms: D020413:3' Untranslated Regions; D000368:Aged; D001665:Binding Sites; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000401:mortality; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: D020413:3' Untranslated Regions; C117307:KRAS protein, human; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; C487931:mirnlet7 microRNA, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins