GERM-LINE BRCA1 MUTATIONS IN JEWISH AND NON-JEWISH WOMEN WITH EARLY-ONSET BREAST-CANCER

Background. Mutations in a germ-line allele of the BRCA1 gene contribu te to the familial breast cancer syndrome. However, the prevalence of these mutations is unknown in women with breast cancer who do not have the features of this familial syndrome. We sought BRCA1 mutations in women who were given a diagnosis of breast cancer at an early age, bec ause early onset is characteristic of a genetic predisposition to canc er. Methods. Clinical information and peripheral-blood mononuclear cel ls were obtained from 418 women from the Boston metropolitan area in w hom breast cancer was diagnosed at or before the age of 40. A comprehe nsive BRCA1 mutational analysis, involving automated nucleotide sequen cing and a protein-truncation assay, was undertaken in 30 of these wom en, who had breast cancer before the age of 30. In addition, the BRCA1 mutation 185delAG, which is prevalent in the Ashkenazi Jewish populat ion, was sought with an allele-specific polymerase-chain-reaction assa y in 39 Jewish women among the 418 women who had breast cancer at or b efore the age of 40. Results. Among 30 women with breast cancer before the age of 30, 4 (13 percent) had definite, chain-terminating mutatio ns and 1 had a missense mutation. Two of the four Jewish women in this cohort had the 185delAG mutation, Among the 39 Jewish women with brea st cancer at or before the age of 40, 8 (21 percent) carried the 185de lAG mutation (95 percent confidence interval, 9 to 36 percent). Conclu sions. Germ-line BRCA1 mutations can be present in young women with br east cancer who do not belong to families with multiple affected membe rs. The specific BRCA1 mutation known as 185delAG is strongly associat ed with the onset of breast cancer in Jewish women before the age of 4 0.