Research Papers:

Fine–mapping of two differentiated thyroid carcinoma susceptibility loci at 2q35 and 8p12 in Europeans, Melanesians and Polynesians

Julie Guibon, Pierre-Emmanuel Sugier, Om Kulkarni, Mojgan Karimi, Delphine Bacq-Daian, Céline Besse, Anne Boland, Elisabeth Adjadj, Frédérique Rachédi, Carole Rubino, Constance Xhaard, Claire Mulot, Pierre Laurent-Puig, Anne-Valérie Guizard, Claire Schvartz, Rosa Maria Ortiz, Yan Ren, Evgenia Ostroumova, Jean-François Deleuze, Marie-Christine Boutron-Ruault, Ausrele Kesminiene, Florent De Vathaire, Pascal Guénel, Fabienne Lesueur and Thérèse Truong _

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Oncotarget. 2021; 12:493-506. https://doi.org/10.18632/oncotarget.27888

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Julie Guibon1,2, Pierre-Emmanuel Sugier1, Om Kulkarni3, Mojgan Karimi1, Delphine Bacq-Daian3, Céline Besse3, Anne Boland3, Elisabeth Adjadj4, Frédérique Rachédi5, Carole Rubino4, Constance Xhaard4,6, Claire Mulot7, Pierre Laurent-Puig7, Anne-Valérie Guizard8,9, Claire Schvartz10, Rosa Maria Ortiz11, Yan Ren4, Evgenia Ostroumova12, Jean-François Deleuze3, Marie-Christine Boutron-Ruault1, Ausrele Kesminiene12, Florent De Vathaire4, Pascal Guénel1, Fabienne Lesueur2,* and Thérèse Truong1,*

1 University Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Exposome and Heredity Team, Villejuif, France

2 Inserm, U900, Institut Curie, PSL University, Mines ParisTech, Paris, France

3 University Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine, Evry, France

4 University Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Epidemiology of Radiations Team, Villejuif, France

5 Endocrinology Unit, Territorial Hospital Taaone, Papeete, French Polynesia

6 University of Lorraine, INSERM CIC 1433, Nancy CHRU, Inserm U1116, FCRIN, INI-CRCT, Nancy, France

7 Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, USPC, Université Paris Descartes, Université Paris Diderot, EPIGENETEC, Paris, France

8 Registre Général des Tumeurs du Calvados, Centre François Baclesse, Caen, France

9 Inserm U1086 -UCN "ANTICIPE", Caen, France

10 Registre des Cancers Thyroïdiens, Institut Godinot, Reims, France

11 Institute of Oncology and Radiobiology, La Havana, Cuba

12 International Agency for Research on Cancer, Lyon, France

* These authors contributed equally to this work

Correspondence to:

Thérèse Truong,email: [email protected]

Keywords: thyroid cancer; cancer genetics; case-control study; fine-mapping study; single nucleotide polymorphism

Received: October 14, 2020     Accepted: January 26, 2021     Published: March 02, 2021

Copyright: © 2021 Guibon et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


Differentiated thyroid carcinoma (DTC) incidence is characterized by wide ethnic and geographic variations, with high incidence rates observed in Oceanian populations. Genome-wide association studies (GWAS) identified mainly four DTC susceptibility loci at 9q22.33, 14q13.3, 2q35 and 8p12. Here we performed fine-mapping of the 2q35 and 8p12 loci in the population of the EPITHYR consortium that includes Europeans, Melanesians and Polynesians to identify likely causal variants for DTC risk. We conducted a colocalization analysis using eQTLs data to determine the SNPs with the highest probability of causality.

At 2q35, we highlighted rs16857609 located in DIRC3. This SNP has a high probability of causality in the three populations, and a significant association in Europeans (OR = 1.4, p = 1.9 x 10-10). It is also associated with expression of DIRC3 and of the nearby gene IGFBP5 in thyroid tumour cells. At 8p12, we identified rs7844425 which was significantly associated with DTC in Europeans (OR = 1.32, p = 7.6 x 10-8) and rs2439304, which was highlighted by the colocalization analysis but only moderately associated with DTC in our dataset (OR = 1.2, p = 0.001). These SNPs are linked to the expression of NRG1 in thyroid tissue.

Hence, our study identified novel variants at 2q35 and 8p12 to be prioritized for further functional studies.

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PII: 27888