Low prevalence of germlineBRCA1 mutations in early onset breast cancer without a family history

• Published in: Journal of medical genetics 2000-10, Vol.37 (10), p.792
• Main Authors: ELLIS, DAVID, GREENMAN, JILL, HODGSON, SHIRLEY, McCALL, SAM, LALLOO, FIONA, CAMERON, JUNE, IZATT, LOUISE, SCOTT, GILLIAN, JACOBS, CHRIS, WATTS, SALLY, CHORLEY, WENDY, PERRETT, CHRIS, MACDERMOT, KAY, MOHAMMED, SHEHLA, EVANS, GARETH, MATHEW, CHRISTOPHER G
• Format: Article
• Language: English
• Subjects: Breast cancer; Family medical history; Health risk assessment; Mutation
• ISSN: 0022-2593; 1468-6244
• DOI: 10.1136/jmg.37.10.792

Studies of the prevalence of germline mutations in BRCA1and BRCA2 in women with breast cancer has enabled the frequency of mutations to be determined in women with different ages at diagnosis and extent of family history of breast cancer. 2 3 The CASH study into the attributable risk of breast and ovarian cancer estimated that 33% of all breast cancers diagnosed by the age of 29 years, and 22% diagnosed by the age of 30-39 years, are the result of an inherited mutation. 4 However, the proportion of breast cancer cases diagnosed by 40 years resulting from a BRCA1 mutation was predicted to be 5.3%. Fitzgerald et al 6 detectedBRCA1 mutations in 13% of women diagnosed before the age of 30 years, but this included Ashkenazi Jewish patients who have founder mutations and some patients with a family history. Since we did not screen the promoter region ofBRCA1 or for deletions of entire exons, 14 we cannot exclude the possibility that some mutations were missed, and the pathogenic status of several sequence variants remains unresolved.