title: Common variants at 9q22.33, 14q13.3, and ATM loci, and risk of differentiated thyroid cancer in the French Polynesian population.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors: Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, F-94800, Villejuif, France; University Paris-Sud, UMRS 1018, F-94807, Villejuif, France; IGR, F-94800, Villejuif, France.
authors: Stéphane
authors: S
authors: Maillard
authors: Genetic Cancer Susceptibility, International Agency for Research on Cancer (IARC), F-69372, Lyon, France; CRCL, CNRS UMR5286, INSERM U1052, Centre Leon Bérard, Lyon, France.
authors: Francesca
authors: F
authors: Damiola
authors: Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, F-94800, Villejuif, France; University Paris-Sud, UMRS 1018, F-94807, Villejuif, France; IGR, F-94800, Villejuif, France.
authors: Enora
authors: E
authors: Clero
authors: Genetic Cancer Susceptibility, International Agency for Research on Cancer (IARC), F-69372, Lyon, France.
authors: Maroulio
authors: M
authors: Pertesi
authors: Genetic Cancer Susceptibility, International Agency for Research on Cancer (IARC), F-69372, Lyon, France.
authors: Nivonirina
authors: N
authors: Robinot
authors: Territorial Hospital Taaone, Papeete, French Polynesia.
authors: Frédérique
authors: F
authors: Rachédi
authors: 10 IPRAME, Papeete, French Polynesia.
authors: Jean-Louis
authors: JL
authors: Boissin
authors: Paofai Clinic, Papeete, French Polynesia.
authors: Joseph
authors: J
authors: Sebbag
authors: Endocrinologist, Papeete, French Polynesia.
authors: Larrys
authors: L
authors: Shan
authors: Territorial Hospital Taaone, Papeete, French Polynesia.
authors: Frédérique
authors: F
authors: Bost-Bezeaud
authors: Laboratoire Boz, Papeete, French Polynesia.
authors: Patrick
authors: P
authors: Petitdidier
authors: Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, F-94800, Villejuif, France; University Paris-Sud, UMRS 1018, F-94807, Villejuif, France; IGR, F-94800, Villejuif, France.
authors: Françoise
authors: F
authors: Doyon
authors: Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, F-94800, Villejuif, France; University Paris-Sud, UMRS 1018, F-94807, Villejuif, France; IGR, F-94800, Villejuif, France.
authors: Constance
authors: C
authors: Xhaard
authors: Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, F-94800, Villejuif, France; University Paris-Sud, UMRS 1018, F-94807, Villejuif, France; IGR, F-94800, Villejuif, France.
authors: Carole
authors: C
authors: Rubino
authors: Fondation Jean Dausset CEPH, F-75010, Paris, France.
authors: Hélène
authors: H
authors: Blanché
authors: Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, DHHS, Bethesda, MD, United States of America.
authors: Vladimir
authors: V
authors: Drozdovitch
authors: Genetic Cancer Susceptibility, International Agency for Research on Cancer (IARC), F-69372, Lyon, France; Inserm, U900, Institut Curie, Mines ParisTech, F-75248, Paris, France.
authors: Fabienne
authors: F
authors: Lesueur
authors: Inserm, Centre for research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, F-94800, Villejuif, France; University Paris-Sud, UMRS 1018, F-94807, Villejuif, France; IGR, F-94800, Villejuif, France.
authors: Florent
authors: F
authors: de Vathaire
mesh_terms: D018263:Adenocarcinoma, Follicular / Q000453:epidemiology / Q000235:genetics*; D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D002291:Carcinoma, Papillary / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D002454:Cell Differentiation; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011114:Polynesia / Q000453:epidemiology; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics*; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors / Q000235:genetics
chemical_list: C106894:FOXE1 protein, human; D051858:Forkhead Transcription Factors; D009687:Nuclear Proteins; D000074482:Thyroid Nuclear Factor 1; D014157:Transcription Factors; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins