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Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes.

Publication ,  Journal Article
Shi, T-Y; Cheng, X; Yu, K-D; Sun, M-H; Shao, Z-M; Wang, M-Y; Zhu, M-L; He, J; Li, Q-X; Chen, X-J; Zhou, X-Y; Wu, X; Wei, Q
Published in: Carcinogenesis
April 2013

Tumor necrosis factor-α-induced protein 8 (TNFAIP8) is an anti apoptotic and pro-oncogenic signaling molecule involved in the process of immunity, carcinogenesis and tumor progression. Single nucleotide polymorphisms (SNPs) at microRNA-binding sites may change messenger RNA target gene function, thus leading to cancer susceptibility and tumor progression. In this study of 1584 cervical cancer cases and 1394 cancer-free female controls, we investigated associations between three potentially functional SNPs in TNFAIP8 family genes and cervical cancer risk as well as platinum resistance and clinical outcomes in Eastern Chinese women. We found that the TNFAIP8-rs11064 variant GG genotype was associated with an increased risk of cervical cancer compared with AA/AG genotypes (adjusted odds ratio = 2.16, 95% confidence interval = 1.16-4.03, P = 0.015). Further in vitro and ex vivo functional experiments demonstrated that the TNFAIP8-rs11064 variant G allele weakened the binding affinity of miR-22 to the TNFAIP8 3'-untranslated region (UTR) in four cancer cell lines, resulting in increased production of the TNFAIP8 protein in the patients' cervical tissues. In the survival subset, the high TNFAIP8 protein expression was significantly associated with both resistance to cisplatin and nedaplatin, recurrence and death from cervical cancer. Taken together, in the absence of information on human papillomavirus (HPV) infection, the TNFAIP8-rs11064 SNP may function by affecting the affinity of miR-22 binding to the 3'-UTR of TNFAIP8 and regulating TNFAIP8 expression, thus contributing to cervical cancer risk. Additionally, the increased TNFAIP8 protein expression may predict platinum resistance and clinical outcomes in cervical cancer patients. Larger, prospective studies with detailed HPV infection data are warranted to validate our findings.

Duke Scholars

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2013

Volume

34

Issue

4

Start / End Page

770 / 778

Location

England

Related Subject Headings

  • Uterine Cervical Neoplasms
  • Risk
  • Polymorphism, Single Nucleotide
  • Paclitaxel
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • MicroRNAs
  • Humans
  • Genotype
  • Genetic Predisposition to Disease
 

Citation

APA
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MLA
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Shi, T.-Y., Cheng, X., Yu, K.-D., Sun, M.-H., Shao, Z.-M., Wang, M.-Y., … Wei, Q. (2013). Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes. Carcinogenesis, 34(4), 770–778. https://doi.org/10.1093/carcin/bgt001
Shi, Ting-Yan, Xi Cheng, Ke-Da Yu, Meng-Hong Sun, Zhi-Ming Shao, Meng-Yun Wang, Mei-Ling Zhu, et al. “Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes.Carcinogenesis 34, no. 4 (April 2013): 770–78. https://doi.org/10.1093/carcin/bgt001.
Shi T-Y, Cheng X, Yu K-D, Sun M-H, Shao Z-M, Wang M-Y, et al. Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes. Carcinogenesis. 2013 Apr;34(4):770–8.
Shi, Ting-Yan, et al. “Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes.Carcinogenesis, vol. 34, no. 4, Apr. 2013, pp. 770–78. Pubmed, doi:10.1093/carcin/bgt001.
Shi T-Y, Cheng X, Yu K-D, Sun M-H, Shao Z-M, Wang M-Y, Zhu M-L, He J, Li Q-X, Chen X-J, Zhou X-Y, Wu X, Wei Q. Functional variants in TNFAIP8 associated with cervical cancer susceptibility and clinical outcomes. Carcinogenesis. 2013 Apr;34(4):770–778.
Journal cover image

Published In

Carcinogenesis

DOI

EISSN

1460-2180

Publication Date

April 2013

Volume

34

Issue

4

Start / End Page

770 / 778

Location

England

Related Subject Headings

  • Uterine Cervical Neoplasms
  • Risk
  • Polymorphism, Single Nucleotide
  • Paclitaxel
  • Organoplatinum Compounds
  • Oncology & Carcinogenesis
  • MicroRNAs
  • Humans
  • Genotype
  • Genetic Predisposition to Disease