title: Functional variations in the ATM gene and susceptibility to differentiated thyroid carcinoma.
abstract: BACKGROUND
  ATM is critical in response to ionizing radiation-induced DNA damage.
  
  
  OBJECTIVE
  Variations in ATM are hypothesized to affect individual susceptibility to thyroid cancer. Our objective was to evaluate the association between ATM polymorphisms and thyroid cancer risk.
  
  
  METHODS
  Six ATM single nucleotide polymorphisms (SNP) were genotyped in two independent case-control series including 592 patients with differentiated thyroid carcinoma (DTC) and 885 healthy individuals. An unconditional logistic regression model was applied to calculate odds ratios (OR) and 95% confidence intervals (CI) for each SNP with respect to risk of DTC and the combination effect of SNP on cancer risk.
  
  
  RESULTS
  The risk-allele frequencies of all the SNP were similar in the two case-control populations. Under a dominant model of inheritance, the G allele of ATM rs189037 exhibited a protective effect against DTC (adjusted OR = 0.8; 95% CI, 0.6-1.0; P = 0.04), and the G allele of rs1800057 was associated with increased risk of DTC (adjusted OR = 1.9; 95% CI, 1.1-3.1; P = 0.02). A protective haplotype (A-G-C-T-C-A) was associated with decreased risk of DTC in non-Hispanic whites (adjusted OR = 0.2; 95% CI, 0.0-0.8; P = 0.03). A significant dose-response relationship was observed between the total number of risk alleles of ATM and DTC risk (P = 0.01). Carriers of a combination of six to seven and eight to 10 risk alleles were at 30% (adjusted OR = 1.3; 95% CI, 1.0-1.7) and 50% (adjusted OR = 1.5; 95% CI, 1.1-2.1) increased risk of DTC, respectively.
  
  
  CONCLUSIONS
  Individual susceptibility to DTC may be attributable to polymorphisms of ATM, and the associations warrant confirmation in independent studies.
authors.affiliation: Departments of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xu
authors.forename: Elaine Cristina
authors.initials: EC
authors.lastname: Morari
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Erich M
authors.initials: EM
authors.lastname: Sturgis
authors.forename: Laura S
authors.initials: LS
authors.lastname: Ward
mesh_terms: D018249:Adenoma, Oxyphilic / Q000453:epidemiology / Q000235:genetics; D000328:Adult; D064007:Ataxia Telangiectasia Mutated Proteins; D002291:Carcinoma, Papillary / Q000453:epidemiology* / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002454:Cell Differentiation / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics; D005838:Genotype; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D013964:Thyroid Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases