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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.    Principal Findings  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.    Significance  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.

Common Variants at 9q22.33, 14q13.3, and ATM Loci, and Risk of Differentiated Thyroid Cancer in the French Polynesian Population