title: Common variants at the 9q22.33, 14q13.3 and ATM loci, and risk of differentiated thyroid cancer in the Cuban population.
abstract: BACKGROUND
  The incidence of differentiated thyroid carcinoma (DTC) in Cuba is low and the contribution of host genetic factors to DTC in this population has not been investigated so far. Our goal was to assess the role of known risk polymorphisms in DTC cases living in Havana. We genotyped five polymorphisms located at the DTC susceptibility loci on chromosome 14q13.3 near NK2 homeobox 1 (NKX2-1), on chromosome 9q22.33 near Forkhead factor E1 (FOXE1) and within the DNA repair gene Ataxia-Telangiectasia Mutated (ATM) in 203 cases and 212 age- and sex- matched controls. Potential interactions between these polymorphisms and other DTC risk factors such as body surface area, body mass index, size, ethnicity, and, for women, the parity were also examined.
  
  
  RESULTS
  Significant association with DTC risk was found for rs944289 near NKX2-1 (OR per A allele = 1.6, 95% CI: 1.2-2.1), and three polymorphisms near or within FOXE1, namely rs965513 (OR per A allele = 1.7, 95% CI: 1.2-2.3), rs1867277 in the promoter region of the gene (OR per A allele = 1.5, 95% CI: 1.1-1.9) and the poly-alanine tract expansion polymorphism rs71369530 (OR per Long Allele = 1.8, 95% CI: 1.3-2.5), only the 2 latter remaining significant when correcting for multiple tests. Overall, no association between DTC and the coding SNP D1853N (rs1801516) in ATM (OR per A Allele = 1.1, 95% CI: 0.7-1.7) was seen. Nevertheless women who had 2 or more pregnancies had a 3.5-fold increase in risk of DTC if they carried the A allele (OR 3.5, 95% CI: 3.2-9.8) as compared to 0.8 (OR 0.8, 95% CI: 0.4-1.6) in those who had fewer than 2.
  
  
  CONCLUSIONS
  We confirmed in the Cuban population the role of the loci previously associated with DTC susceptibility in European and Japanese populations through genome-wide association studies. Our results on ATM and the number of pregnancies raise interesting questions on the mechanisms by which oestrogens, or other hormones, alter the DNA damage response and DNA repair through the regulation of key effector proteins such as ATM. Due to the small size of our study and to multiple tests, all these results warrant further investigation.
authors: Institute of Oncology and Radiobiology, Havana, Cuba. celiam@infomed.sld.cu.
authors: Celia M
authors: CM
authors: Pereda
authors: The French National Institute of Health and Medical Research (Inserm), U900, Institut Curie, Mines ParisTech, Paris, F-75005, France. fabienne.lesueur@curie.fr.|Genetic Cancer Susceptibility, International Agency for Research on Cancer (IARC), Lyon, F-69372, France. fabienne.lesueur@curie.fr.
authors: Fabienne
authors: F
authors: Lesueur
authors: Genetic Cancer Susceptibility, International Agency for Research on Cancer (IARC), Lyon, F-69372, France. PertesiM@fellows.iarc.fr.
authors: Maroulio
authors: M
authors: Pertesi
authors: Genetic Cancer Susceptibility, International Agency for Research on Cancer (IARC), Lyon, F-69372, France. robinotn@iarc.fr.
authors: Nivonirina
authors: N
authors: Robinot
authors: Institute of Oncology and Radiobiology, Havana, Cuba. lence@infomed.sld.cu.
authors: Juan J
authors: JJ
authors: Lence-Anta
authors: National Institute of Endocrinology, Havana, Cuba. silviaelena@infomed.sld.cu.
authors: Silvia
authors: S
authors: Turcios
authors: Institute of Oncology and Radiobiology, Havana, Cuba. milagros.velasco@infomed.sld.cu.
authors: Milagros
authors: M
authors: Velasco
authors: Institute of Oncology and Radiobiology, Havana, Cuba. maechappe@infomed.sld.cu.
authors: Mae
authors: M
authors: Chappe
authors: Cuban Health Public Ministry, Havana, Cuba. idalmis@infomed.sld.cu.
authors: Idalmis
authors: I
authors: Infante
authors: Institute of Oncology and Radiobiology, Havana, Cuba. marlene.bustillo@infomed.sld.cu.
authors: Marlene
authors: M
authors: Bustillo
authors: Institute of Oncology and Radiobiology, Havana, Cuba. anabel.garcia@infomed.sld.cu.
authors: Anabel
authors: A
authors: García
authors: The French National Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, 94805, France. enora.clero@irsn.fr.|Paris-Sud University, Villejuif, 94805, France. enora.clero@irsn.fr.|Institut Gustave Roussy (IGR), Villejuif, 94805, France. enora.clero@irsn.fr.
authors: Enora
authors: E
authors: Clero
authors: The French National Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, 94805, France. constance.xhaard@gustaveroussy.fr.|Paris-Sud University, Villejuif, 94805, France. constance.xhaard@gustaveroussy.fr.|Institut Gustave Roussy (IGR), Villejuif, 94805, France. constance.xhaard@gustaveroussy.fr.
authors: Constance
authors: C
authors: Xhaard
authors: The French National Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, 94805, France. yan.ren@gustaveroussy.fr.|Paris-Sud University, Villejuif, 94805, France. yan.ren@gustaveroussy.fr.|Institut Gustave Roussy (IGR), Villejuif, 94805, France. yan.ren@gustaveroussy.fr.
authors: Yan
authors: Y
authors: Ren
authors: The French National Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, 94805, France. maillard.steph@gmail.com.|Paris-Sud University, Villejuif, 94805, France. maillard.steph@gmail.com.|Institut Gustave Roussy (IGR), Villejuif, 94805, France. maillard.steph@gmail.com.
authors: Stéphane
authors: S
authors: Maillard
authors: CRCL, CNRS UMR5286, the French National Institute of Health and Medical Research (Inserm) U1052, Centre Léon Bérard, Lyon, F-69008, France. francesca.damiola@lyon.unicancer.fr.
authors: Francesca
authors: F
authors: Damiola
authors: The French National Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, 94805, France. carole.rubino@gustaveroussy.fr.|Paris-Sud University, Villejuif, 94805, France. carole.rubino@gustaveroussy.fr.|Institut Gustave Roussy (IGR), Villejuif, 94805, France. carole.rubino@gustaveroussy.fr.
authors: Carole
authors: C
authors: Rubino
authors: Institute of Oncology and Radiobiology, Havana, Cuba. sirced.salazar@infomed.sld.cu.
authors: Sirced
authors: S
authors: Salazar
authors: Cuban Health Public Ministry, Havana, Cuba. regla.rodriguez@infomed.sld.cu.
authors: Regla
authors: R
authors: Rodriguez
authors: Institute of Oncology and Radiobiology, Havana, Cuba. rmortiz@infomed.sld.cu.
authors: Rosa M
authors: RM
authors: Ortiz
authors: The French National Institute of Health and Medical Research (Inserm), Centre for Research in Epidemiology and Population Health (CESP), U1018, Radiation Epidemiology Group, Villejuif, 94805, France. florent.devathaire@gustaveroussy.fr.|Paris-Sud University, Villejuif, 94805, France. florent.devathaire@gustaveroussy.fr.|Institut Gustave Roussy (IGR), Villejuif, 94805, France. florent.devathaire@gustaveroussy.fr.
authors: Florent
authors: F
authors: de Vathaire
mesh_terms: D000483:Alleles; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D002883:Chromosomes, Human, Pair 14; D002899:Chromosomes, Human, Pair 9; D003462:Cuba / Q000453:epidemiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D060787:Neoplasm Grading; D011110:Polymorphism, Genetic; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012306:Risk; D013964:Thyroid Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology*
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins