Observed frequencies of FOXE1 multi-allelic poly-alanine tract alleles (rs71369530) in the Polynesian population.

<p>Observed frequencies of FOXE1 multi-allelic poly-alanine tract alleles (rs71369530) in the Polynesian population.</p

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

<div><p>Background</p><p>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 <i>ATM</i>, to the risk of differentiated thyroid cancer (DTC) in 177 cases and 275 matched controls from the native population.</p><p>Principal Findings</p><p>For the GWAS SNP rs965513 near <i>FOXE1</i>, 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 <i>FOXE1</i>, while no association was observed with rs1867277 falling in the promoter region of the gene. In contrast, the GWAS SNP rs944289 (<i>NKX2-1</i>) did not show any significant association. Although the missense substitution D1853N (rs1801516) in <i>ATM</i> 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.</p><p>Significance</p><p>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 <i>FOXE1</i> rs965513, the direction of association and the effect size was similar to that observed in other populations, whereas for <i>ATM</i> rs1801516, the minor allele was associated to an increased risk in the Polynesian population and with a decreased risk in the European population.</p></div

Association results between the five polymorphisms and the risk of developing DTC.

<p>^a Stratified by age and sex.</p><p>^b Stratified by age and sex, and adjusted on BMI, BSA ethnicity, and thyroid radiation dose received before age 15 years.</p><p>^c Multiplicative model of inheritance.</p><p>^d Dominant model of inheritance (combined heterozygotes and rare homozygotes <i>versus</i> common homozygotes).</p><p>^e Recessive model of inheritance (rare homozygotes <i>versus</i> combined heterozygotes and common homozygotes).</p><p>^f S for alleles coding for 12–14 alanines and L for alleles coding for 16–19 alanines.</p><p>Association results between the five polymorphisms and the risk of developing DTC.</p

Characteristics of the 602 participants of the case-control study, born and resident in French Polynesia, and of the sub-group included in the genetic study.

<p>Characteristics of the 602 participants of the case-control study, born and resident in French Polynesia, and of the sub-group included in the genetic study.</p

Description of the five studied polymorphisms.

<p>Description of the five studied polymorphisms.</p