Common variants at 9q22.33, 14q13.3, and ATM loci, and risk of differentiated thyroid cancer in the French Polynesian population.

PLoS ONE. 2015;10(4):e0123700 DOI 10.1371/journal.pone.0123700

 

Journal Homepage

Journal Title: PLoS ONE

ISSN: 1932-6203 (Online)

Publisher: Public Library of Science (PLoS)

LCC Subject Category: Medicine | Science

Country of publisher: United States

Language of fulltext: English

Full-text formats available: PDF, HTML, XML

 

AUTHORS


Stéphane Maillard

Francesca Damiola

Enora Clero

Maroulio Pertesi

Nivonirina Robinot

Frédérique Rachédi

Jean-Louis Boissin

Joseph Sebbag

Larrys Shan

Frédérique Bost-Bezeaud

Patrick Petitdidier

Françoise Doyon

Constance Xhaard

Carole Rubino

Hélène Blanché

Vladimir Drozdovitch

Fabienne Lesueur

Florent de Vathaire

EDITORIAL INFORMATION

Peer review

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Instructions for authors

Time From Submission to Publication: 24 weeks

 

Abstract | Full Text

French Polynesia has one of the highest incidence rates of thyroid cancer worldwide. Relationships with the atmospheric nuclear weapons tests and other environmental, biological, or behavioral factors have already been reported, but genetic susceptibility has yet to be investigated. We assessed the contribution of polymorphisms at the 9q22.33 and 14q13.3 loci identified by GWAS, and within the DNA repair gene ATM, to the risk of differentiated thyroid cancer (DTC) in 177 cases and 275 matched controls from the native population.For the GWAS SNP rs965513 near FOXE1, an association was found between genotypes G/A and A/A, and risk of DTC. A multiplicative effect of allele A was even noted. An excess risk was also observed in individuals carrying two long alleles of the poly-alanine tract expansion in FOXE1, while no association was observed with rs1867277 falling in the promoter region of the gene. In contrast, the GWAS SNP rs944289 (NKX2-1) did not show any significant association. Although the missense substitution D1853N (rs1801516) in ATM was rare in the population, carriers of the minor allele (A) also showed an excess risk. The relationships between these five polymorphisms and the risk of DTC were not contingent on the body surface area, body mass index, ethnicity or dietary iodine intake. However, an interaction was evidenced between the thyroid radiation dose and rs944289.A clear link could not be established between the high incidence in French Polynesia and the studied polymorphisms, involved in susceptibility to DTC in other populations. Important variation in allele frequencies was observed in the Polynesian population as compared to the European populations. For FOXE1 rs965513, the direction of association and the effect size was similar to that observed in other populations, whereas for ATM rs1801516, the minor allele was associated to an increased risk in the Polynesian population and with a decreased risk in the European population.