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Increased frequency of ATM mutations in breast carcinoma patients with early onset disease and positive family history
Author(s) -
Teraoka Sharon N.,
Malone Kathleen E.,
Doody David R.,
Suter Nicola M.,
Ostrander Elaine A.,
Daling Janet R.,
Concan Patrick
Publication year - 2001
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(20010801)92:3<479::aid-cncr1346>3.0.co;2-g
Subject(s) - missense mutation , breast carcinoma , ataxia telangiectasia , medicine , family history , breast cancer , carcinoma , mutation , germline mutation , incidence (geometry) , oncology , population , genetics , pathology , gene , cancer , biology , dna damage , dna , physics , environmental health , optics
BACKGROUND An increased incidence of breast carcinoma has been reported among relatives of individuals who are affected with the rare recessive disorder, ataxia‐telangiectasia (A‐T), and who are heterozygous for mutations in the ataxia‐telangiectasia mutated ( ATM ) gene. However, most studies of breast carcinoma cases from the general population have failed to find a higher incidence of ATM mutations in cases when compared with controls. METHODS Genomic DNA samples from 258 individuals were screened for mutations of all types in each of the 62 coding exons of the ATM gene; 142 of these were from breast carcinoma cases with a first‐degree family history or early age at diagnosis, 35 were from cases selected for the presence of either known disease‐related mutations ( n = 25) or missense alterations of unknown consequences ( n = 10) in BRCA1 or BRCA2 , and 81 were from matched controls. RESULTS A total of 12 individuals with ATM mutations were identified, 11 among 142 breast carcinoma cases (7.7%; 95% CI , 3.9–13.4%) and 1 among 81 controls (1.2%; 95% CI , 0.0–6.7%) ( P = 0.06). All mutations detected were of the missense type; none were predicted to truncate the ATM protein. Among cases, mutations were found exclusively in patients with a family history of breast carcinoma (12.1%; 95% CI , 6.2–20.6%) (P = 0.02). Similar frequencies of ATM mutations were found in 35 additional cases selected for the presence of BRCA1 or BRCA2 mutations when compared with cases overall. CONCLUSIONS ATM mutations, specifically missense mutations, are more common in breast carcinoma cases selected for first‐degree family history and early age at diagnosis. Cancer 2001;92:479–87. © 2001 American Cancer Society.