Skip to main content
SpringerLink
Log in

TITF1 and TITF2 loci variants indicate significant associations with thyroid cancer

  • Meta-Analysis
  • Published:
Endocrine Aims and scope Submit manuscript

Abstract

A number of studies have investigated the influence of TITF1 and TITF2 genetic variants on thyroid carcinogenesis, but their associations remain unclear due to the controversial results. The objective of this study was to test the hypothesis that TITF1 and TITF2 variants modulate thyroid cancer susceptibility. Eligible studies were identified through online searches supplemented by manual search. Either the DerSimonian and Laird method or the Mantel–Haenszel method was used to estimate the risk of thyroid cancer (ORs and 95 % CIs). The pooled ORs were calculated assuming the allele model. We identified a total of 10 publications concerning the topic of interest. Overall, meta-analysis of rs944289 showed 1.11-fold increased risk of thyroid cancer related to the risk T allele (T vs. C: OR 1.11, 95 % CI 1.05–1.17). For rs965513, individuals carrying the risk A allele, compared to individuals with the G allele, had 31 % higher risk of thyroid cancer (A vs. G: OR 1.31, 95 % CI 1.17–1.46). Analyses in total samples for rs1867277, rs1443434, and rs907580 yielded similar associations (A vs. G: OR 1.22, 95 % CI 1.06–1.39; G vs. T: OR 1.26, 95 % CI 1.09–1.45; T vs. C: OR 1.42, 95 % CI 1.21–1.66, respectively). The significant association persisted among Caucasians in subgroup analyses for rs944289 and rs965513. The genetic susceptibility of thyroid cancer seems likely to be associated with the risk allele at rs944289 in the TITF1 gene and at rs1867277, rs965513, rs1443434, and rs907580 in the TITF2 gene.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

References

  1. G. Pellegriti, F. Frasca, C. Regalbuto, S. Squatrito, R. Vigneri, Worldwide increasing incidence of thyroid cancer: update on epidemiology and risk factors. J. Cancer Epidemiol. 2013, 965212 (2013)

    Article  PubMed Central  PubMed  Google Scholar 

  2. Surveillance, Epidemiology, and End Results Program 2011 SEER*Stat Database: SEER 9 Registry Research Data, (1973–2008) National Cancer Institute, DCCPS, Surveillance Research Program, Cancer Statistics Branch. www.seer.cancer.gov

  3. L. Agate, L. Lorusso, R. Elisei, New and old knowledge on differentiated thyroid cancer epidemiology and risk factors. J. Endocrinol. Invest. 35, 3–9 (2012)

    CAS  PubMed  Google Scholar 

  4. E. Clero, F. Doyon, V. Chungue, F. Rachedi, J.L. Boissin et al., Dietary iodine and thyroid cancer risk in French Polynesia: a case-control study. Thyroid 22, 422–429 (2012)

    Article  CAS  PubMed  Google Scholar 

  5. M.A. Cannizzaro, M. Veroux, M. Costanzo, A. Buffone, V. Okatyeva, Radiation exposure and thyroid cancer. Ann. Ital. Chir. 83, 369–372 (2012)

    PubMed  Google Scholar 

  6. D.E. Goldgar, D.F. Easton, L.A. Cannon-Albright, M.H. Skolnick, Systematic population-based assessment of cancer risk in first-degree relatives of cancer probands. J. Natl. Cancer Inst. 86, 1600–1608 (1994)

    Article  CAS  PubMed  Google Scholar 

  7. K. Hemminki, P. Vaittinen, Effect of paternal and maternal cancer on cancer in the offspring: a population-based study. Cancer Epidemiol. Biomarkers Prev. 6, 993–997 (1997)

    CAS  PubMed  Google Scholar 

  8. M.G. Perna, D. Civitareale, V. De Filippis, M. Sacco, C. Cisternino et al., Absence of mutations in the gene encoding thyroid transcription factor-1 (TTF-1) in patients with thyroid dysgenesis. Thyroid 7, 377–381 (1997)

    Article  CAS  PubMed  Google Scholar 

  9. N. Dathan, R. Parlato, A. Rosica, M. De Felice, R. Di Lauro, Distribution of the titf2/foxe1 gene product is consistent with an important role in the development of foregut endoderm, palate, and hair. Dev. Dyn. 224, 450–456 (2002)

    Article  CAS  PubMed  Google Scholar 

  10. R. Parlato, A. Rosica, A. Rodriguez-Mallon, A. Affuso, M.P. Postiglione et al., An integrated regulatory network controlling survival and migration in thyroid organogenesis. Dev. Biol. 276, 464–475 (2004)

    Article  CAS  PubMed  Google Scholar 

  11. H. Francis-Lang, M. Zannini, M. De Felice, M.T. Berlingieri, A. Fusco et al., Multiple mechanisms of interference between transformation and differentiation in thyroid cells. Mol. Cell. Biol. 12, 5793–5800 (1992)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  12. J. Gudmundsson, P. Sulem, D.F. Gudbjartsson, J.G. Jonasson, A. Sigurdsson et al., Common variants on 9q22.33 and 14q13.3 predispose to thyroid cancer in European populations. Nat. Genet. 41, 460–464 (2009)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. F. Damiola, G. Byrnes, M. Moissonnier, M. Pertesi, I. Deltour et al., Contribution of ATM and FOXE1 (TTF2) to risk of papillary thyroid carcinoma in Belarusian children exposed to radiation. Int. J. Cancer 134, 1659–1668 (2014)

    Article  CAS  PubMed  Google Scholar 

  14. J. Lau, J.P. Ioannidis, C.H. Schmid, Quantitative synthesis in systematic reviews. Ann. Intern. Med. 127, 820–826 (1997)

    Article  CAS  PubMed  Google Scholar 

  15. J.P. Higgins, S.G. Thompson, J.J. Deeks, D.G. Altman, Measuring inconsistency in meta-analyses. BMJ 327, 557–560 (2003)

    Article  PubMed Central  PubMed  Google Scholar 

  16. R. DerSimonian, R. Kacker, Random-effects model for meta-analysis of clinical trials: an update. Contemp. Clin. Trials 28, 105–114 (2007)

    Article  PubMed  Google Scholar 

  17. N. Mantel, W. Haenszel, Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl. Cancer Inst. 22, 719–748 (1959)

    CAS  PubMed  Google Scholar 

  18. M. Egger, G. Davey Smith, M. Schneider, C. Minder, Bias in meta-analysis detected by a simple, graphical test. BMJ 315, 629–634 (1997)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  19. M. Matsuse, M. Takahashi, N. Mitsutake, E. Nishihara, M. Hirokawa et al., The FOXE1 and NKX2-1 loci are associated with susceptibility to papillary thyroid carcinoma in the Japanese population. J. Med. Genet. 48, 645–648 (2011)

    Article  CAS  PubMed  Google Scholar 

  20. M. Takahashi, V.A. Saenko, T.I. Rogounovitch, T. Kawaguchi, V.M. Drozd et al., The FOXE1 locus is a major genetic determinant for radiation-related thyroid carcinoma in Chernobyl. Hum. Mol. Genet. 19, 2516–2523 (2010)

    Article  CAS  PubMed  Google Scholar 

  21. C.J.Y. Liu, C. Chen, C.Z. Sun, M. Zhao, Correlation of FOXE1 gene polymorphism with papilliary thyroid carcinoma in Yunnan China. J. Mod. Oncol. 9, 1958–1963 (2013)

    Google Scholar 

  22. M. Penna-Martinez, F. Epp, H. Kahles, E. Ramos-Lopez, N. Hinsch et al., FOXE1 association with differentiated thyroid cancer and its progression. Thyroid 24, 845–851 (2014)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  23. R.A. Tomaz, I. Sousa, J.G. Silva, C. Santos, M.R. Teixeira et al., FOXE1 polymorphisms are associated with familial and sporadic nonmedullary thyroid cancer susceptibility. Clin. Endocrinol. (Oxf) 77, 926–933 (2012)

    Article  CAS  Google Scholar 

  24. I. Landa, S. Ruiz-Llorente, C. Montero-Conde, L. Inglada-Perez, F. Schiavi et al., The variant rs1867277 in FOXE1 gene confers thyroid cancer susceptibility through the recruitment of USF1/USF2 transcription factors. PLoS Genet. 5, e1000637 (2009)

    Article  PubMed Central  PubMed  Google Scholar 

  25. M. Bullock, E.L. Duncan, C. O’Neill, L. Tacon, M. Sywak et al., Association of FOXE1 polyalanine repeat region with papillary thyroid cancer. J. Clin. Endocrinol. Metab. 97, E1814–E1819 (2012)

    Article  CAS  PubMed  Google Scholar 

  26. A.M. Jones, K.M. Howarth, L. Martin, M. Gorman, R. Mihai et al., Thyroid cancer susceptibility polymorphisms: confirmation of loci on chromosomes 9q22 and 14q13, validation of a recessive 8q24 locus and failure to replicate a locus on 5q24. J. Med. Genet. 49, 158–163 (2012)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. T. Kusakabe, A. Kawaguchi, N. Hoshi, R. Kawaguchi, S. Hoshi et al., Thyroid-specific enhancer-binding protein/NKX2.1 is required for the maintenance of ordered architecture and function of the differentiated thyroid. Mol. Endocrinol. 20, 1796–1809 (2006)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. S. Kimura, Y. Hara, T. Pineau, P. Fernandez-Salguero, C.H. Fox et al., The T/ebp null mouse: thyroid-specific enhancer-binding protein is essential for the organogenesis of the thyroid, lung, ventral forebrain, and pituitary. Genes Dev. 10, 60–69 (1996)

    Article  CAS  PubMed  Google Scholar 

  29. L. Perrone, M. Pasca di Magliano, M. Zannini, R. Di Lauro, The thyroid transcription factor 2 (TTF-2) is a promoter-specific DNA-binding independent transcriptional repressor. Biochem. Biophys. Res. Commun. 275, 203–208 (2000)

    Article  CAS  PubMed  Google Scholar 

  30. I. Cuesta, K.S. Zaret, P. Santisteban, The forkhead factor FoxE1 binds to the thyroperoxidase promoter during thyroid cell differentiation and modifies compacted chromatin structure. Mol. Cell. Biol. 27, 7302–7314 (2007)

    Article  PubMed Central  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

No current funding sources for this study.

Conflict of interest

The authors have declared that no competing interests exist.

Author information

Authors and Affiliations

  1. Department of Oncology and Southwest Cancer Center, Southwest Hospital Third Military Medical University, 29 Gaotanyan Main Street, Chongqing, 400038, China

    Peiliang Geng, Juanjuan Ou, Jianjun Li, Yunmei Liao, Ning Wang, Ganfeng Xie, Rina Sa, Chen Liu, Lisha Xiang & Houjie Liang

Authors
  1. Peiliang Geng
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Juanjuan Ou
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jianjun Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yunmei Liao
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ning Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ganfeng Xie
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Rina Sa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Chen Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Lisha Xiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Houjie Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Houjie Liang.

Additional information

Peiliang Geng and Juanjuan Ou are co-first author.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Geng, P., Ou, J., Li, J. et al. TITF1 and TITF2 loci variants indicate significant associations with thyroid cancer. Endocrine 50, 598–607 (2015). https://doi.org/10.1007/s12020-015-0664-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12020-015-0664-0

Keywords

Search

Navigation