title: ATM haplotypes and breast cancer risk in Jewish high-risk women.
abstract: While genetic factors clearly play a role in conferring breast cancer risk, the contribution of ATM gene mutations to breast cancer is still unsettled. To shed light on this issue, ATM haplotypes were constructed using eight SNPs spanning the ATM gene region (142 kb) in ethnically diverse non-Ashkenazi Jewish controls (n=118) and high-risk (n=142) women. Of the 28 haplotypes noted, four were encountered in frequencies of 5% or more and accounted for 85% of all haplotypes. Subsequently, ATM haplotyping of high-risk, non-Ashkenazi Jews was performed on 66 women with breast cancer and 76 asymptomatic. One SNP (rs228589) was significantly more prevalent among breast cancer cases compared with controls (P=4 x 10(-9)), and one discriminative ATM haplotype was significantly more prevalent among breast cancer cases (33.3%) compared with controls (3.8%), (P< or =10(-10)). There was no significant difference in the SNP and haplotype distribution between asymptomatic high-risk and symptomatic women as a function of disease status. We conclude that a specific ATM SNP and a specific haplotype are associated with increased breast cancer risk in high-risk non-Ashkenazi Jews.
authors.affiliation: 1Susanne Levy Gertner Oncogenetics Unit, The Danek Gertner Institute of Human Genetics, Tel-Hashomer, Israel.
authors.forename: M
authors.initials: M
authors.lastname: Koren
authors.forename: G
authors.initials: G
authors.lastname: Kimmel
authors.forename: E
authors.initials: E
authors.lastname: Ben-Asher
authors.forename: I
authors.initials: I
authors.lastname: Gal
authors.forename: M Z
authors.initials: MZ
authors.lastname: Papa
authors.forename: J S
authors.initials: JS
authors.lastname: Beckmann
authors.forename: D
authors.initials: D
authors.lastname: Lancet
authors.forename: R
authors.initials: R
authors.lastname: Shamir
authors.forename: E
authors.initials: E
authors.lastname: Friedman
mesh_terms: D000328:Adult; D000368:Aged; D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D016022:Case-Control Studies; D018797:Cell Cycle Proteins / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007557:Israel / Q000208:ethnology; D007585:Jews / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012307:Risk Factors; 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