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Genetic variants in selected pre‐microRNA genes and the risk of squamous cell carcinoma of the head and neck
Author(s) -
Liu Zhensheng,
Li Guojun,
Wei Sheng,
Niu Jiangong,
ElNaggar Adel. K.,
Sturgis Erich M.,
Wei Qingyi
Publication year - 2010
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.25323
Subject(s) - medicine , microrna , head and neck , gene , basal cell , head and neck squamous cell carcinoma , genetics , oncology , head and neck cancer , cancer research , cancer , pathology , biology , surgery
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. Cancer 2010. © 2010 American Cancer Society.