title: Association of common ATM variants with familial breast cancer in a South American population.
abstract: BACKGROUND
  The ATM gene has been frequently involved in hereditary breast cancer as a low-penetrance susceptibility gene but evidence regarding the role of ATM as a breast cancer susceptibility gene has been contradictory.
  
  
  METHODS
  In this study, a full mutation analysis of the ATM gene was carried out in patients from 137 Chilean breast cancer families, of which 126 were BRCA1/2 negatives and 11 BRCA1/2 positives. We further perform a case-control study between the subgroup of 126 cases BRCA1/2 negatives and 200 controls for the 5557G>A missense variant and the IVS38-8T>C and the IVS24-9delT polymorphisms.
  
  
  RESULTS
  In the full mutation analysis we detected two missense variants and eight intronic polymorphisms. Carriers of the variant IVS24-9delT, or IVS38-8T>C, or 5557G>A showed an increase in breast cancer risk. The higher significance was observed in the carriers of IVS38-8T>C (OR = 3.09 [95%CI 1.11-8.59], p = 0.024). The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype confered a 3.19 fold increase in breast cancer risk (OR = 3.19 [95%CI 1.16-8.89], p = 0.021). The haplotype estimation suggested a strong linkage disequilibrium between the three markers (D' = 1). We detected only three haplotypes in the cases and control samples, some of these may be founder haplotypes in the Chilean population.
  
  
  CONCLUSIONS
  The IVS24-9 T/(-T), IVS38-8 T/C, 5557 G/A composite genotype alone or in combination with certain genetic background and/or environmental factors, could modify the cancer risk by increasing genetic instability or by altering the effect of the normal DNA damage response.
authors.affiliation: Human Genetics Program, Institute of Biomedical Sciences (ICBM), School of Medicine, University of Chile, Chile. pgonzalez@med.uchile.cl
authors.forename: Patricio
authors.initials: P
authors.lastname: González-Hormazábal
authors.forename: Teresa
authors.initials: T
authors.lastname: Bravo
authors.forename: Rafael
authors.initials: R
authors.lastname: Blanco
authors.forename: Carlos Y
authors.initials: CY
authors.lastname: Valenzuela
authors.forename: Fernando
authors.initials: F
authors.lastname: Gómez
authors.forename: Enrique
authors.initials: E
authors.lastname: Waugh
authors.forename: Octavio
authors.initials: O
authors.lastname: Peralta
authors.forename: Waldo
authors.initials: W
authors.lastname: Ortuzar
authors.forename: Jose M
authors.initials: JM
authors.lastname: Reyes
authors.forename: Lilian
authors.initials: L
authors.lastname: Jara
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D002677:Chile; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D006801:Humans; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases / 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