TY - JOUR
T1 - A functional variant at the miR-184 binding site in TNFAIP2 and risk of squamous cell carcinoma of the head and neck
AU - Liu, Zhensheng
AU - Wei, Sheng
AU - Ma, Hongxia
AU - Zhao, Mei
AU - Myers, Jeffrey N.
AU - Weber, Randal S.
AU - Sturgis, Erich M.
AU - Wei, Qingyi
PY - 2011/11
Y1 - 2011/11
N2 - Although the role of TNFAIP2 is still unclear, it is an important gene involved in apoptosis, and there are single-nucleotide polymorphisms (SNPs) at its microRNA (miRNA)-binding sites that could modulate miRNA target gene function. In this study, we evaluated associations of four selected SNPs (rs8126 T > C, rs710100 G > A, rs1052912 G > A and rs1052823 G > T) in the miRNA-binding sites of the 3' untranslated region (UTR) with squamous cell carcinoma of the head and neck (SCCHN) risk in 1077 patients with SCCHN and 1073 cancer-free controls in a non-Hispanic White population. We found that, compared with the rs8126 TT genotype, the variant C allele were associated with increased SCCHN risk in an allele dose-response manner (adjusted odds ratio = 1.48 and 95% confidence interval = 1.06-2.05 for CC, respectively; P trend = 0.009). No significant associations were seen for the other three SNPs (rs710100 G > A, rs1052912 G > A and rs1052823 G > T). Additionally, we identified that the rs8126 T > C SNP is within the miR-184 seed binding region in the 3' UTR of TNFAIP2. Further functional analyses showed that the rs8126 variant C allele led to significantly lower luciferase activity, compared with the T allele. In the genotype-phenotype correlation analysis of peripheral blood mononuclear cells from 64 SCCHN patients, the rs8126 CC genotype was associated with reduced expression of TNFAIP2 messenger RNA. Taken together, these findings indicate that the miR-184 binding site SNP (rs8126 T > C) in the 3' UTR of TNFAIP2 is functional by modulating TNFAIP2 expression and contributes to SCCHN susceptibility. Larger replication studies are needed to confirm our findings.
AB - Although the role of TNFAIP2 is still unclear, it is an important gene involved in apoptosis, and there are single-nucleotide polymorphisms (SNPs) at its microRNA (miRNA)-binding sites that could modulate miRNA target gene function. In this study, we evaluated associations of four selected SNPs (rs8126 T > C, rs710100 G > A, rs1052912 G > A and rs1052823 G > T) in the miRNA-binding sites of the 3' untranslated region (UTR) with squamous cell carcinoma of the head and neck (SCCHN) risk in 1077 patients with SCCHN and 1073 cancer-free controls in a non-Hispanic White population. We found that, compared with the rs8126 TT genotype, the variant C allele were associated with increased SCCHN risk in an allele dose-response manner (adjusted odds ratio = 1.48 and 95% confidence interval = 1.06-2.05 for CC, respectively; P trend = 0.009). No significant associations were seen for the other three SNPs (rs710100 G > A, rs1052912 G > A and rs1052823 G > T). Additionally, we identified that the rs8126 T > C SNP is within the miR-184 seed binding region in the 3' UTR of TNFAIP2. Further functional analyses showed that the rs8126 variant C allele led to significantly lower luciferase activity, compared with the T allele. In the genotype-phenotype correlation analysis of peripheral blood mononuclear cells from 64 SCCHN patients, the rs8126 CC genotype was associated with reduced expression of TNFAIP2 messenger RNA. Taken together, these findings indicate that the miR-184 binding site SNP (rs8126 T > C) in the 3' UTR of TNFAIP2 is functional by modulating TNFAIP2 expression and contributes to SCCHN susceptibility. Larger replication studies are needed to confirm our findings.
UR - http://www.scopus.com/inward/record.url?scp=80755187828&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80755187828&partnerID=8YFLogxK
U2 - 10.1093/carcin/bgr209
DO - 10.1093/carcin/bgr209
M3 - Article
C2 - 21934093
AN - SCOPUS:80755187828
SN - 0143-3334
VL - 32
SP - 1668
EP - 1674
JO - Carcinogenesis
JF - Carcinogenesis
IS - 11
ER -