Genetic factors for differentiated thyroid cancer in French Polynesia: new candidate loci

Author:

Zidane Monia1,Haber Marc23,Truong Thérèse4,Rachédi Frédérique5,Ory Catherine6,Chevillard Sylvie6,Blanché Hélène7,Olaso Robert8,Boland Anne8,Conte Éric9,Karimi Mojgan4,Ren Yan1,Xhaard Constance10,Souchard Vincent1,Gardon Jacques11,Taquet Marc12,Bouville André13,Deleuze Jean-François78,Drozdovitch Vladimir14,de Vathaire Florent1,Cazier Jean-Baptiste23

Affiliation:

1. University Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Team "Radiations Epidemiology" , Villejuif 94805 , France

2. Centre for Computational Biology, University of Birmingham , Birmingham B152TT , UK

3. Institute of Cancer and Genomic Sciences, University of Birmingham , Birmingham B152TT , UK

4. University Paris-Saclay, UVSQ, Inserm, Gustave Roussy, CESP, Team "Exposome and Heredity" , Villejuif 94805 , France

5. Endocrinology Unit, Territorial Hospital Taaone, F-98713, Papeete , Tahiti 98713 , French Polynesia

6. CEA, Laboratoire de Cancérologie Fondamentale, Institut de Biologie François Jacob, iRCM, SREIT, Laboratoire de Cancérologie Expérimentale (LCE), Université Paris-Saclay , Fontenay aux Roses 92265 , France

7. Fondation Jean Dausset-Centre d'Etude du Polymorphisme Humain , Paris 75010 , France

8. Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine , Evry 91057 , France

9. U.S.R. 2003 (CNRS / UPF), Faa'a , Tahiti 98702 , France

10. University of Lorraine, INSERM CIC 1433, Nancy CHRU, INSERM U1116 , Nancy 54500 , France

11. Hydrosciences Montpellier, Research Institute for Development, CNRS, University of Montpellier , Montpellier 62307 , France

12. Research Institute for Development, Center IRD on Tahiti, Arue , Tahiti 98713 , French Polynesia

13. National Cancer Institute (retired) , Bethesda, MD 20892 , USA

14. Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS , Bethesda, MD 20892 , USA

Abstract

Abstract Background Populations of French Polynesia (FP), where France performed atmospheric tests between 1966 and 1974, experience a high incidence of differentiated thyroid cancer (DTC). However, up to now, no sufficiently large study of DTC genetic factors in this population has been performed to reach definitive conclusion. This research aimed to analyze the genetic factors of DTC risk among the native FP populations. Methods We analyzed more than 300 000 single nucleotide polymorphisms (SNPs) genotyped in 283 DTC cases and 418 matched controls born in FP, most being younger than 15 years old at the time of the first nuclear tests. We analyzed the genetic profile of our cohort to identify population subgroups. We then completed a genome-wide analysis study on the whole population. Results We identified a specific genetic structure in the FP population reflecting admixture from Asian and European populations. We identified three regions associated with increased DTC risk at 6q24.3, 10p12.2, and 17q21.32. The lead SNPs at these loci showed respective p-values of 1.66 × 10−7, 2.39 × 10−7, and 7.19 × 10−7 and corresponding odds ratios of 2.02, 1.89, and 2.37. Conclusion Our study results suggest a role of the loci 6q24.3, 10p12.2 and 17q21.32 in DTC risk. However, a whole genome sequencing approach would be better suited to characterize these factors than genotyping with microarray chip designed for the Caucasian population. Moreover, the functional impact of these three new loci needs to be further explored and validated.

Funder

Institut National Du Cancer

Fondation ARC

Publisher

Oxford University Press (OUP)

Subject

General Medicine

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