Regular Article

British Journal of Cancer (1999) 79, 34–39. doi:10.1038/sj.bjc.6690008 www.bjcancer.com
Published online 11 December 1998

BRCA1 mutations and other sequence variants in a population-based sample of Australian women with breast cancer

M C Southey1,2, A A Tesoriero1, C R Andersen1, K M Jennings1, S M Brown1, G S Dite3, M A Jenkins3, R H Osborne3, J A Maskiell3, L Porter4, G G Giles5, M R E McCredie4,6, J L Hopper3 and D J Venter1,2

  1. 1Department of Pathology and Research, Peter MacCallum Cancer Institute, Melbourne, Victoria 3000, Australia
  2. 2Department of Pathology, The University of Melbourne, Parkville, Victoria 3052, Australia
  3. 3The University of Melbourne, Genetic Epidemiology Unit, 200 Berkeley Street, Carlton, Victoria 3053, Australia
  4. 4Cancer and Epidemiology Research Unit, New South Wales Cancer Council, Woolloomooloo, NSW 2011, Australia
  5. 5Cancer Epidemiology Centre, The Anti-Cancer Council of Victoria, Carlton, Victoria 3053, Australia
  6. 6Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand

Correspondence: JL Hopper, The University of Melbourne, Genetic Epidemiology Unit, 200 Berkeley Street, Carlton, Victoria 3053, Australia

Received 4 February 1998; Revised 7 May 1998; Accepted 12 May 1998.

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Abstract

The frequency, in women with breast cancer, of mutations and other variants in the susceptibility gene, BRCA1, was investigated using a population-based case–control-family study. Cases were women living in Melbourne or Sydney, Australia, with histologically confirmed, first primary, invasive breast cancer, diagnosed before the age of 40 years, recorded on the state Cancer Registries. Controls were women without breast cancer, frequency-matched for age, randomly selected from electoral rolls. Full manual sequencing of the coding region of BRCA1 was conducted in a randomly stratified sample of 91 cases; 47 with, and 44 without, a family history of breast cancer in a first- or second-degree relative. All detected variants were tested in a random sample of 67 controls. Three cases with a (protein-truncating) mutation were detected. Only one case had a family history; her mother had breast cancer, but did not carry the mutation. The proportion of Australian women with breast cancer before age 40 who carry a germline mutation in BRCA1 was estimated to be 3.8% (95% Cl 0.3–12.6%). Seven rare variants were also detected, but for none was there evidence of a strong effect on breast cancer susceptibility. Therefore, on a population basis, rare variants are likely to contribute little to breast cancer incidence.

Keywords:

BRCA1, breast cancer, DNA sequencing, mutations, population prevalence, variants

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