A functional TNFAIP2 3'-UTR rs8126 genetic polymorphism contributes to risk of esophageal squamous cell carcinoma.
BACKGROUND
Accumulated evidences demonstrated that single nucleotide polymorphisms (SNPs) in mRNA 3'-untranslated region (3'-UTR) may impact microRNAs (miRNAs)-mediated expression regulation of oncogenes and tumor suppressors. There is a TNFAIP2 3'-UTR rs8126 T>C genetic variant which has been proved to be associated with head and neck cancer susceptibility. This SNP could disturb binding of miR-184 with TNFAIP2 mRNA and influence TNFAIP2 regulation. However, it is still unclear how this polymorphism is involved in development of esophageal squamous cell carcinoma (ESCC). Therefore, we hypothesized that the functional TNFAIP2 rs8126 SNP may affect TNFAIP2 expression and, thus, ESCC risk.


METHODS
We investigated the association between the TNFAIP2 rs8126 variant and ESCC risk as well as the functional relevance on TNFAIP2 expression in vivo. Genotypes were determined in a case-control set consisted of 588 ESCC patients and 600 controls. The allele-specific regulation on TNFAIP2 expression by the rs8126 SNP was examined in normal and cancerous tissue specimens of esophagus.


RESULTS
We found that individuals carrying the rs8126 CC or CT genotype had an OR of 1.89 (95%CI  = 1.23-2.85, P = 0.003) or 1.38 (95%CI  = 1.05-1.73, P = 0.017) for developing ESCC in Chinese compared with individual carrying the TT genotype. Carriers of the rs8126 CC and CT genotypes had significantly lower TNFAIP2 mRNA levels than those with the TT genotypes in normal esophagus tissues (P<0.05).


CONCLUSIONS
Our data demonstrate that functional TNFAIP2 rs8126 genetic variant is a ESCC susceptibility SNP. These results support the hypothesis that genetic variants interrupting miRNA-mediated gene regulation might be important genetic modifiers of cancer risk.
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Jian
J
Zhang
Qingdao Qilu Hospital, Shandong University, Qingdao, Shandong Province, China.
Hongchen
H
Yu
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Yi
Y
Zhang
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Xiaoshi
X
Zhang
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Guixin
G
Zheng
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Yang
Y
Gao
Department of Clinical Laboratory, Qilu Hospital of Shandong University, Jinan, Shandong Province, China.
Chuanxin
C
Wang
Department of Radiation Oncology, Huaian No. 2 Hospital, Huaian, Jiangsu Province, China.
Liqing
L
Zhou
D020413:3' Untranslated Regions / Q000235:genetics*; D044466:Asian People / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D016207:Cytokines / Q000235:genetics*; D004938:Esophageal Neoplasms / Q000235:genetics*; D000077277:Esophageal Squamous Cell Carcinoma; D005838:Genotype; D006801:Humans; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
D020413:3' Untranslated Regions; D016207:Cytokines; C085839:TNFAIP2 protein, human