Genetic variants in selected pre-microRNA genes and the risk of squamous cell carcinoma of the head and neck.


Journal Article

BACKGROUND: Single nucleotide polymorphisms (SNPs) in microRNAs (miRNAs) may alter the processing, transcription, and expression of miRNAs and, thus, may contribute to cancer development. The authors hypothesized that common polymorphisms in pre-miRNAs are associated individually and (more likely) collectively with the risk of squamous cell carcinoma of the head and neck (SCCHN). METHODS: The authors genotyped 4 common polymorphisms in pre-miRNAs: Homo sapiens miRNA 146a (hsa-mir-146a) (reference SNP 2910164 [rs2910164]; guanine to cytosine [G→C]), hsa-mir-149 (rs2292832; guanine to thymine [G→T]), hsa-mir-196a2 (rs11614913; C→T), and hsa-mir-499 (rs3746444; adenine to guanine [A→G]) in 1109 patients with SCCHN (cases) and in 1130 cancer-free patients (controls) in a non-Hispanic white population that was frequency-matched by age and sex. Univariate and multivariate logistic regression models were used to calculate crude and adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Of the 4 SNPs that were studied, the hsa-mir-499 AG and GG genotypes were associated with a reduced risk of SCCHN (OR, 0.83; 95% CI, 0.69-0.99). When the 4 SNPs were combined according to putative risk genotype, the number of observed risk genotypes was associated with an increased risk of SCCHN in a dose-response manner with ORs of 1.0, 1.20, and 1.40 for individuals who had 0 or 1 risk genotypes, 2 or 3 risk genotypes, and 4 risk genotypes, respectively (P(trend) = .037). Specifically, the risk was 1.23-fold (95% CI, 0.98-fold to 1.56-fold) for individuals with 2 to 4 risk genotypes and 1.40-fold (95% CI, 1.02-fold to 1.92-fold) for individuals who had 4 risk genotypes compared with individuals who had 0 or 1 risk genotypes. This risk was more pronounced in men and in patients with oropharyngeal cancer. CONCLUSIONS: The combined risk genotypes of 4 common SNPs in pre-miRNAs were associated significantly with a moderately increased risk of SCCHN. Larger studies are needed to validate the current findings.

Full Text

Duke Authors

Cited Authors

  • Liu, Z; Li, G; Wei, S; Niu, J; El-Naggar, AK; Sturgis, EM; Wei, Q

Published Date

  • October 15, 2010

Published In

Volume / Issue

  • 116 / 20

Start / End Page

  • 4753 - 4760

PubMed ID

  • 20549817

Pubmed Central ID

  • 20549817

International Standard Serial Number (ISSN)

  • 0008-543X

Digital Object Identifier (DOI)

  • 10.1002/cncr.25323


  • eng

Conference Location

  • United States