Abstract
For families with a small number of cases of breast and/or ovarian cancer, limited data are available to predict the likelihood of genetic predisposition due to mutations in BRCA1 or BRCA2. In 104 families with three or more affected individuals (average 3.8) seeking counselling at family cancer clinics, mutation analysis was performed in the open reading frame of BRCA1 and BRCA2 by the protein truncation test and mutation-specific assays. In 31 of the 104 families tested, mutations were detected (30%). The majority of these mutations (25) occurred in BRCA1. Mutations were detected in 15 out of 25 families (60%) with both breast and ovarian cancer and in 16 out of 79 families (20%) with exclusively cases of breast cancer. Thus, an ovarian cancer case strongly predicted finding a mutation (P < 0.001). Within the group of small breast-cancer-only families, a bilateral breast cancer case or a unilateral breast cancer case diagnosed before age 40 independently predicted finding a BRCA1 or BRCA2 mutation (P = 0.005 and P = 0.02, respectively). Therefore, even small breast/ovarian cancer families with at least one case of ovarian cancer, bilateral breast cancer, or a case of breast cancer diagnosed before age 40, should be referred for mutation screening. © 1999 Cancer Research Campaign
Keywords: breast cancer, ovarian cancer, bilateral breast cancer, BRCA1, BRCA2
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- Couch F. J., DeShano M. L., Blackwood M. A., Calzone K., Stopfer J., Campeau L., Ganguly A., Rebbeck T., Weber B. L. BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med. 1997 May 15;336(20):1409–1415. doi: 10.1056/NEJM199705153362002. [DOI] [PubMed] [Google Scholar]
- Easton D. F., Bishop D. T., Ford D., Crockford G. P. Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium. Am J Hum Genet. 1993 Apr;52(4):678–701. [PMC free article] [PubMed] [Google Scholar]
- Hogervorst F. B., Cornelis R. S., Bout M., van Vliet M., Oosterwijk J. C., Olmer R., Bakker B., Klijn J. G., Vasen H. F., Meijers-Heijboer H. Rapid detection of BRCA1 mutations by the protein truncation test. Nat Genet. 1995 Jun;10(2):208–212. doi: 10.1038/ng0695-208. [DOI] [PubMed] [Google Scholar]
- Krainer M., Silva-Arrieta S., FitzGerald M. G., Shimada A., Ishioka C., Kanamaru R., MacDonald D. J., Unsal H., Finkelstein D. M., Bowcock A. Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. N Engl J Med. 1997 May 15;336(20):1416–1421. doi: 10.1056/NEJM199705153362003. [DOI] [PubMed] [Google Scholar]
- Miki Y., Swensen J., Shattuck-Eidens D., Futreal P. A., Harshman K., Tavtigian S., Liu Q., Cochran C., Bennett L. M., Ding W. A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science. 1994 Oct 7;266(5182):66–71. doi: 10.1126/science.7545954. [DOI] [PubMed] [Google Scholar]
- Peelen T., van Vliet M., Petrij-Bosch A., Mieremet R., Szabo C., van den Ouweland A. M., Hogervorst F., Brohet R., Ligtenberg M. J., Teugels E. A high proportion of novel mutations in BRCA1 with strong founder effects among Dutch and Belgian hereditary breast and ovarian cancer families. Am J Hum Genet. 1997 May;60(5):1041–1049. [PMC free article] [PubMed] [Google Scholar]
- Petrij-Bosch A., Peelen T., van Vliet M., van Eijk R., Olmer R., Drüsedau M., Hogervorst F. B., Hageman S., Arts P. J., Ligtenberg M. J. BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet. 1997 Nov;17(3):341–345. doi: 10.1038/ng1197-341. [DOI] [PubMed] [Google Scholar]
- Petrij-Bosch A., Peelen T., van Vliet M., van Eijk R., Olmer R., Drüsedau M., Hogervorst F. B., Hageman S., Arts P. J., Ligtenberg M. J. BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet. 1997 Nov;17(3):341–345. doi: 10.1038/ng1197-341. [DOI] [PubMed] [Google Scholar]
- Shattuck-Eidens D., Oliphant A., McClure M., McBride C., Gupte J., Rubano T., Pruss D., Tavtigian S. V., Teng D. H., Adey N. BRCA1 sequence analysis in women at high risk for susceptibility mutations. Risk factor analysis and implications for genetic testing. JAMA. 1997 Oct 15;278(15):1242–1250. [PubMed] [Google Scholar]
- Szabo C. I., King M. C. Population genetics of BRCA1 and BRCA2. Am J Hum Genet. 1997 May;60(5):1013–1020. [PMC free article] [PubMed] [Google Scholar]
- Tavtigian S. V., Simard J., Rommens J., Couch F., Shattuck-Eidens D., Neuhausen S., Merajver S., Thorlacius S., Offit K., Stoppa-Lyonnet D. The complete BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet. 1996 Mar;12(3):333–337. doi: 10.1038/ng0396-333. [DOI] [PubMed] [Google Scholar]
- Wooster R., Bignell G., Lancaster J., Swift S., Seal S., Mangion J., Collins N., Gregory S., Gumbs C., Micklem G. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995 Dec 21;378(6559):789–792. doi: 10.1038/378789a0. [DOI] [PubMed] [Google Scholar]
- Wooster R., Neuhausen S. L., Mangion J., Quirk Y., Ford D., Collins N., Nguyen K., Seal S., Tran T., Averill D. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994 Sep 30;265(5181):2088–2090. doi: 10.1126/science.8091231. [DOI] [PubMed] [Google Scholar]