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. 2009 Jun;30(6):1003-7.
doi: 10.1093/carcin/bgp099. Epub 2009 Apr 20.

A let-7 microRNA-binding Site Polymorphism in the KRAS 3' UTR Is Associated With Reduced Survival in Oral Cancers

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Free PMC article

A let-7 microRNA-binding Site Polymorphism in the KRAS 3' UTR Is Associated With Reduced Survival in Oral Cancers

Brock C Christensen et al. Carcinogenesis. .
Free PMC article

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.

Figures

Fig. 1.
Fig. 1.
Kaplan–Meier survival probability plots stratified by KRAS-LCS6 genotype for head and neck tumors with available staging data. Survival time is defined as time from diagnosis to death or last known follow-up where crosses represent censored values. The log-rank method was used to test for a difference between strata. Solid lines represent cases with wild-type KRAS-LCS6 genotype; dotted lines represent cases carrying any KRAS-LCS6 variant alleles. (A) All tumor sites, n = 344, P = 0.20. (B) Oral cancers, n = 190, P = 0.06. (C) Pharyngeal cancers, n = 91, P = 0.65. (D) Laryngeal cancers, n = 63, P = 0.83.

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