BRCA1-related breast cancer in Austrian breast and ovarian cancer families: specific BRCA1 mutations and pathological characteristics

Int J Cancer. 1998 Jul 29;77(3):354-60. doi: 10.1002/(sici)1097-0215(19980729)77:3<354::aid-ijc8>3.0.co;2-n.

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.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Austria
  • BRCA1 Protein / chemistry
  • BRCA1 Protein / genetics
  • Breast Neoplasms / genetics*
  • Breast Neoplasms / mortality
  • Breast Neoplasms / pathology
  • Carcinoma, Ductal, Breast / genetics
  • Carcinoma, Lobular / genetics
  • Carcinoma, Medullary / genetics
  • DNA Transposable Elements
  • Family
  • Female
  • Frameshift Mutation
  • Genes, BRCA1*
  • Humans
  • Lymphatic Metastasis
  • Middle Aged
  • Mutation*
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • Ovarian Neoplasms / genetics*
  • Point Mutation
  • Receptors, Estrogen / analysis
  • Receptors, Progesterone / analysis
  • Recurrence
  • Sequence Deletion
  • Survival Rate

Substances

  • BRCA1 Protein
  • DNA Transposable Elements
  • Receptors, Estrogen
  • Receptors, Progesterone