title: ATM variants 7271T>G and IVS10-6T>G among women with unilateral and bilateral breast cancer.
abstract: Recent reports suggest that two ATM gene mutations, 7271T>G and IVS10-6T>G, are associated with a high risk of breast cancer among multiple-case families. To assess the importance of these two mutations in another 'high-risk' group, young women (under age 51) with multiple primaries, we screened a large population-based series of young women with bilateral breast cancer and compared the frequency of these mutations among similar women diagnosed with unilateral breast cancer. The 1149 women included were enrolled in an ongoing population-based case-control study of the genetic factors that contribute to bilateral breast cancer; they were not selected on the basis of family history of cancer. Screening for 7271T>G and IVS10-6T>G ATM gene mutations was conducted using DHPLC followed by direct sequencing. The 7271T>G mutation was detected in one out of 638 (0.2%) women with unilateral breast cancer and in none of the bilateral cases, and the IVS10-6T>G mutation in one out of 511 (0.2%) bilateral and in eight out of 638 (1.3%) unilateral breast cancer cases. Carriers of either mutation were not limited to women with a family history. Given the likelihood that young women with bilateral breast cancer have a genetic predisposition, the observed mutation distribution is contrary to that expected if these two mutations were to play an important role in breast carcinogenesis among individuals at high risk.
authors.affiliation: Department of Community and Preventive Medicine, Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1043, New York, NY 10029-6574, USA. jonine.bernstein@mssm.edu
authors.forename: J L
authors.initials: JL
authors.lastname: Bernstein
authors.forename: L
authors.initials: L
authors.lastname: Bernstein
authors.forename: W D
authors.initials: WD
authors.lastname: Thompson
authors.forename: C F
authors.initials: CF
authors.lastname: Lynch
authors.forename: K E
authors.initials: KE
authors.lastname: Malone
authors.forename: S L
authors.initials: SL
authors.lastname: Teitelbaum
authors.forename: J H
authors.initials: JH
authors.lastname: Olsen
authors.forename: H
authors.initials: H
authors.lastname: Anton-Culver
authors.forename: J D
authors.initials: JD
authors.lastname: Boice
authors.forename: B S
authors.initials: BS
authors.lastname: Rosenstein
authors.forename: A-L
authors.initials: AL
authors.lastname: Børresen-Dale
authors.forename: R A
authors.initials: RA
authors.lastname: Gatti
authors.forename: P
authors.initials: P
authors.lastname: Concannon
authors.forename: R W
authors.initials: RW
authors.lastname: Haile
mesh_terms: D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D016350:Leucine Zippers; D008403:Mass Screening; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics* / Q000473:pathology*; D010375:Pedigree; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; D025521:Tumor Suppressor Proteins
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human