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Carcinogenesis Advance Access originally published online on April 20, 2009
Carcinogenesis 2009 30(6):1003-1007; doi:10.1093/carcin/bgp099
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© The Author 2009. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

A let-7 microRNA-binding site polymorphism in the KRAS 3' UTR is associated with reduced survival in oral cancers

Brock C. Christensen1,2, Benjamin J. Moyer1, Michele Avissar1, Lauren G. Ouellet1, Silvia L. Plaza1, Michael D. McClean3, Carmen J. Marsit1 and Karl T. Kelsey1,2,*

1 Department of Pathology and Laboratory Medicine
2 Department of Community Health, Center for Environmental Health and Technology, Brown University, Providence, RI 02912, USA
3 Department of Environmental Health, Boston University School of Public Health, Boston, MA 02118, USA

* To whom correspondence should be addressed. Tel: +1 401 863 6420; Fax: +1 401 863 9008; Email: karl_kelsey{at}brown.edu

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.

Abbreviations: CI, confidence interval; HNSCC, head and neck squamous cell carcinoma; HPV, human papillomavirus; HR, hazard ratio; miRNA, microRNA; NSCLC, non-small cell lung cancer; OR, odds ratio; SNP, single nucleotide polymorphism; UTR, untranslated region

Received February 4, 2009; revised March 23, 2009; accepted April 15, 2009.


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