An allelic variant at the ATM locus is implicated in breast cancer susceptibility.
We have tested a simple procedure, disease association by locus stratification, for identifying breast cancer patients with pathogenetic allelic variants at several candidate loci. The strategy was based on the assumption of epistatic interactions of the candidates. We analyzed 66 independent cases from sib pairs affected with breast cancer that had previously been collected during an investigation of pathogenetic-allele-sharing at the HRAS1 mini-satellite locus. An exon 24 polymorphism of ATM, substituting arginine for proline was associated with breast cancer in these cases with an overall odds ratio of 4.5 (95% confidence interval, 1.2-20.5, nominal p = 0.02, 2-tail Fisher exact test). In the presence of a rare HRAS1 allele, the odds ratio increased to 6.9 (95% CI, 1.2-38.3, p = 0.03). Thus, our procedure identified at least one allelic variant of ATM associated with breast cancer, and indicated that the ATM locus may interact with HRAS1.
Larson
G P
GP
Division of Molecular Medicine, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA 91010, USA.
Zhang
G
G
Ding
S
S
Foldenauer
K
K
Udar
N
N
Gatti
R A
RA
Neuberg
D
D
Lunetta
K L
KL
Ruckdeschel
J C
JC
Longmate
J
J
Flanagan
S
S
Krontiris
T G
TG
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001260:Ataxia Telangiectasia / Q000235:genetics; D064007:Ataxia Telangiectasia Mutated Proteins; D001943:Breast Neoplasms / Q000235:genetics*; D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D005091:Exons; D005260:Female; D011905:Genes, ras; D014644:Genetic Variation; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D017346:Protein Serine-Threonine Kinases; D011506:Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D011506:Proteins; D025521:Tumor Suppressor Proteins; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases