title: BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics.
abstract: We identified 17 BRCA1 mutations in 86 Austrian breast and ovarian cancer families (20%) that were screened for mutations by denaturing high-performance liquid chromatography (DHPLC) and the protein truncation test (PTT). Eleven distinct mutations were detected, 4 of them (962del4, 2795del4, 3135del4 and L3376stop) not previously reported in families of non-Austrian origin. In addition, 6 rare missense mutations (allele frequency < 1%) with unknown biological effects were identified. Four mutations occurred more than once in the Austrian population: 2795del4 (3 times), Cys61Gly (3 times) 5382insC (2 times) and Q1806stop (2 times). Haplotype analysis of the 4 recurrent mutations suggested a common ancestor for each of these. Thirty-four breast cancer cases from 17 families with BRCA1 mutations were further analyzed. We observed a low median age of onset (39.5 years). Sixty-eight percent of all BRCA1 breast cancer cases had negative axillary lymph nodes. This group showed a significant prevalence of a negative estrogen and progesterone receptor status and stage I tumors compared with an age-related, node-negative control group. The prevalence of grade III tumors was marginally significant. Survival analysis either with a control group matched for age (within 5 years), grade, histologic subtype and estrogen receptor status, or with an age-related, node-negative comparison group, showed no statistical difference.
authors.affiliation: Department of Obstetrics and Gynecology, University of Vienna, Austria. Teresa.Wagner@akh-wien.ac.at
authors.forename: T M
authors.initials: TM
authors.lastname: Wagner
authors.forename: R A
authors.initials: RA
authors.lastname: Möslinger
authors.forename: D
authors.initials: D
authors.lastname: Muhr
authors.forename: G
authors.initials: G
authors.lastname: Langbauer
authors.forename: K
authors.initials: K
authors.lastname: Hirtenlehner
authors.forename: H
authors.initials: H
authors.lastname: Concin
authors.forename: W
authors.initials: W
authors.lastname: Doeller
authors.forename: A
authors.initials: A
authors.lastname: Haid
authors.forename: A H
authors.initials: AH
authors.lastname: Lang
authors.forename: P
authors.initials: P
authors.lastname: Mayer
authors.forename: E
authors.initials: E
authors.lastname: Ropp
authors.forename: E
authors.initials: E
authors.lastname: Kubista
authors.forename: B
authors.initials: B
authors.lastname: Amirimani
authors.forename: T
authors.initials: T
authors.lastname: Helbich
authors.forename: A
authors.initials: A
authors.lastname: Becherer
authors.forename: O
authors.initials: O
authors.lastname: Scheiner
authors.forename: H
authors.initials: H
authors.lastname: Breiteneder
authors.forename: A
authors.initials: A
authors.lastname: Borg
authors.forename: P
authors.initials: P
authors.lastname: Devilee
authors.forename: P
authors.initials: P
authors.lastname: Oefner
authors.forename: C
authors.initials: C
authors.lastname: Zielinski
mesh_terms: D000328:Adult; D001317:Austria; D019313:BRCA1 Protein / Q000737:chemistry / Q000235:genetics; D001943:Breast Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics; D018275:Carcinoma, Lobular / Q000235:genetics; D018276:Carcinoma, Medullary / Q000235:genetics; D004251:DNA Transposable Elements; D005190:Family; D005260:Female; D016368:Frameshift Mutation; D019398:Genes, BRCA1; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D009154:Mutation; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000235:genetics*; D017354:Point Mutation; D011960:Receptors, Estrogen / Q000032:analysis; D011980:Receptors, Progesterone / Q000032:analysis; D012008:Recurrence; D017384:Sequence Deletion; D015996:Survival Rate
chemical_list: D019313:BRCA1 Protein; D004251:DNA Transposable Elements; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone