title: ATM allelic variants associated to hereditary breast cancer in 94 Chilean women: susceptibility or ethnic influences?
abstract: Besides BRCA1 and BRCA2, two genes accounting for a small proportion of breast cancer cases, ATM has been widely proposed as a low-penetrance susceptibility gene. Several nucleotide changes have been proposed to be associated with breast cancer, still remaining a high controversy in this sense. We screened the ATM gene in 94 breast cancer patients selected from 78 high-risk families, not presenting a mutation in BRCA1 or BRCA2. We found three novel allelic variants: IVS64 + 51delT and p.L752L, not showing association with hereditary breast cancer, and p.L694L found in one family in two breast cancer patients. Two amino acid substitutions p.S707P and p.F858L, previously reported to be associated with breast cancer, were present in our study in cases and controls, lacking of association with breast cancer. A positive association of c.5557G>A (p.D1853N) was found (OR 2.52, P = 0.008), when analyzed alone and in combination with an intronic variant IVS24-9delT (OR 3.97; P = 0.0003). We postulate that our discrepancies with other reports related to the associated ATM alleles to hereditary breast cancer, as well as discrepancies in the literature between other groups, could be explained by the diversity in the ethnic origins of families gathered in a sole study, and the selection of the control group. In relation to this issue, and based on genetic markers, we found that the Chilean group of breast cancer families in this study has a stronger European genetic component than our control sample selected randomly from the Chilean population.
authors.affiliation: Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Teresa
authors.initials: T
authors.lastname: Tapia
authors.forename: Alejandro
authors.initials: A
authors.lastname: Sanchez
authors.forename: Maricarmen
authors.initials: M
authors.lastname: Vallejos
authors.forename: Carolina
authors.initials: C
authors.lastname: Alvarez
authors.forename: Mauricio
authors.initials: M
authors.lastname: Moraga
authors.forename: Susan
authors.initials: S
authors.lastname: Smalley
authors.forename: Mauricio
authors.initials: M
authors.lastname: Camus
authors.forename: Manuel
authors.initials: M
authors.lastname: Alvarez
authors.forename: Pilar
authors.initials: P
authors.lastname: Carvallo
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000208:ethnology* / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology; D002677:Chile; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000502:physiology; D005091:Exons; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease; D006801:Humans; D007438:Introns; D008875:Middle Aged; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000502:physiology
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