Abstract
Approximately 7% of breast cancer and 10% of ovarian cancer in the United States is thought to be due to the presence of an autosomal dominant susceptibility allele. Two breast cancer susceptibility genes (BRCA1 and BRCA2) now have been identified (Miki et al. 1994; Wooster et al. 1995; Tavtigian et al. 1996) and a third (BRCA3) is being actively sought. Breast cancer susceptibility in families with mutations in these genes appears as an autosomal dominant trait, with breast cancer affecting as many as half of the women in each generation. Thus, both of these genes are considered high penetrance genes, as the majority of individuals with these alterations will ultimately develop breast cancer. Mutations in several other high penetrance genes, such as p53 (associated with Li-Fraumeni syndrome) and MSH2 (associated with hereditary non-polyposis colon cancer) also have been identified as causes of hereditary breast cancer, but are extremely rare in the general population. It is very likely that many other genes contribute to inherited breast cancer susceptibility in families where the incidence of breast cancer is elevated, but where the appearance of breast cancer is more scattered, because fewer numbers of carriers will develop breast cancer as a result of these lower penetrance genes. These genetic alterations are complex and what little is known about candidates for low penetrance cancer susceptibility genes is not yet of clinical use.
Adapted from Blackwood MA, Weber BL (1998) Breast cancer genetics: past, present and future. J Clin Oncol, in press
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References
Abeliovich D, Kaduri L, Lerer I et al (1997) The founder mutations 185 del AG and 5382 in sC in BRCA1 and 6174 del T in BRCA2 appear in 60% of ovarian cancer and 30% of early-onset breast cancer patients among Ashkenazi women. Am J Hum Genet 60:505–514
Berman DB, Wagner-Costalas J, Schultz DC et al (1996) Two distinct origins of a common BRCA1 mutation in breast-ovarian cancer families: a genetic study of 15 185delAG mutation kindreds. Am J Hum Genet 58:1166
Berry DA, Parmigiani G, Sanchez J et al (1997) Probability of carrying a mutation of breast-ovarian cancer gene BRCA1 based on family history. J Natl Cancer Inst 89:227–238
Couch FJ, Farid LM, DeShano ML et al (1996) BRCA2 germline mutations in male breast cancer cases and breast cancer families. Nat Genet 13:123–125
Couch FJ, DeShano M, Blackwood MA et al (1997) BRCA1 mutations in women attending clinics that evaluate the risk of breast cancer. N Engl J Med 336:1409–1415
Easton DF, Bishop DT, Ford D et al (1993) Genetic linkage analysis in familial breast and ovarian cancer — results from 214 families. Am J Hum Genet 52:678–701
Easton DF, Bishop DT, Ford D et al (1994) Breast and ovarian cancer incidence in BRCA1 mutation carriers. Lancet 343:962
Eisinger F, Stoppa-Lyonnet D, Longy M et al (1996) Germline mutation at BRCA1 affects the histoprognostic grade in hereditary breast cancer. Cancer Res 56:471
Ford D, Easton DF, Bishop DT et al (1994) Risk of cancer in BRCA1 mutation carriers. Lancet 343:962
Gayther SA, Warren W, Mazoyer S et al (1995) Germline mutations of the BRCA1 gene in breast/ovarian cancer families provide evidence for a genotype/phenotype correlation. Nat Genet 10:208
Hall JM, Lee MK, Newman B et al (1990) Linkage of early onset breast cancer to chromosome 17q21. Science 250:1684
Holt JT, Thompson ME, Szabo C et al (1996) Growth retardation and tumour inhibition by BRCA1. Nat Genet 12:298
Hosking L, Trowsdale J, Nicolai H et al (1995) A somatic BRCA1 mutation in an ovarian tumor. Nat Genet 9:343
Hoskins KF, Stopfer JE, Calzone KA et al (1995) Assessment and counseling for familial cancer risk: a guide for clinicians. JAMA 273:577–585
Lakahani SR, Sloane JP, Gusterson BA et al (1998) The pathology of familial breast cancer: evidence for differences between breast cancers developing in carriers of BRCA1 mutations, BRCA2 mutations, and sporadic cases. Lancet (in press)
Lancaster JM, Wooster R, Mangion J et al (1996) BRCA2 mutations in primary breast and ovarian cancers. Nat Genet 13:238–240
Marcus JN, Watson P, Page DL et al (1996) Hereditary breast cancer: pathobiology, prognosis, and BRCA1 and BRCA2 gene linkage. Cancer 77:697
Matsushima M, Kobayashi K, Erni M et al (1995) Mutation analysis of the BRCA1 gene in 76 Japanese ovarian cancer patients: four germline mutations, but no evidence of somatic mutation. Hum Mol Genet 4:1953
Merajver SD, Pham TM, Caduff RF et al (1995) Somatic mutations in the BRCA1 gene in sporadic ovarian tumors. Nat Genet 9:439
Miki Y, Swensen J, Shattuck-Eidens D et al (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266:66
Miki Y, Katagiri T, Kasumi F et al (1996) Mutation analysis on the BRCA2 gene in primary breast cancers. Nat Genet 13:245–247
Neuhausen SL, Gilewski T, Norton LJ et al (1996a) Recurrent BRCA2 6174delT mutations in Ashkenazi Jewish woman affected by breast cancer. Nat Genet 13:126–128
Neuhausen SL, Mazoyer S, Friedman L et al (1996b) Haplotype and phenotype analysis of six recurrent BRCA1 mutations in 61 families: results of an international study. Am J Hum Genet 58:271–280
Phelan CM, Lancaster JM, Tonin P et al (1996) Mutation analysis of the BRCA2 gene in 49 site-specific breast cancer families. Nat Genet 13:120–122
Piver MS, Jishi MF, Tsukada Y et al (1993) Primary peritoneal carcinoma after prophylactic oophorectomy in women with a family history of ovarian cancer. Cancer 71:2751–2755
Roa BB, Boyd AA, Vblcik K et al (1996) Ashkenazi Jewish population frequency for common mutations in BRCA1 and BRCA2. Nat Genet 14:185–190
Rubin SC, Benjamin I, Behbakht K et al (1996) Clinical and pathological features of ovarian cancer in women with germline mutations of BRCA1. N Engl J Med 19:1413–1416
Serova OM, Mazoyer S, Puget N et al (1997) Mutations in BRCA1 and BRCA2 in breast cancer families: are there more breast cancer-susceptibility genes? Am J Hum Genet 60:486–495
Shattuck-Eidens D, Oliphant A, McClure M et al (1998) Complete DNA sequence analysis of BRCA1: 798 woman at high risk for susceptibility mutations. JAMA (in press)
Sobol H, Stoppa-Lyonnet D, Bressac-de-Paillerets B et al (1996) Truncation at conserved terminal regions of BRCA1 protein is associated with highly proliferating hereditary breast cancers. Cancer Res 56:3126
Streuwing JP, Abeliovitch D, Peterz T et al (1995a) The carrier frequency of the BRCA1 185delAG mutation is approximately 1 percent in Ashkenazi Jewish individuals. Nat Genet 11:198
Streuwing JP, Watson P, Easton DF et al (1995b) Prophylactic oophorectomy in inherited breast/ovarian cancer families. J Natl Cancer Inst 17:33–35
Streuwing JP, Hartge P, Wacholder S et al (1997) Cancer risk with 185delAG and 5382insC mutations of BRCA1 and the 6174delT mutation of BRCA2 among Ashkenazi Jews. N Engl J Med 336:1401–1408
Takahashi H, Behbakht K, McGovern PE et al (1995) Mutation analysis of the BRCA1 gene in ovarian cancers. Cancer Res 55:2998
Takahashi H, Chin HC, Bandera CA et al (1996) Mutations of the BRCA2 gene in ovarian carcinomas. Cancer Res 56:2738–2741
Tavtigian SV, Sinard J, Romens J et al (1996) The BRCA2 gene and mutations in chromosome 13q-linked kindreds. Nat Genet 12:333
Teng DHF, Bogden R, Mitchell J et al (1996) Low incidence of BRCA2 in breast carcinoma and other cancers. Nat Genet 13:241–244
Tonin P, Serova O, Lenoir G et al (1995) BRCA1 mutations in Ashkenazi Jewish women. Am J Hum Genet 57:189
Tonin P, Weber B, Offit K et al (1996) Frequency of recurrent BRCA1 and BRCA2 mutations in Ashkenazi Jewish breast cancer families. Nat Med 2:1179–1183
Wooster R, Neuhausen S, Mangion J et al (1994) Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12–13. Science 265:2088
Wooster R, Bignell G, Lancaster J et al (1995) Identification of the breast cancer susceptibility gene BRCA2. Nature 378:789
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Weber, B.L. (1998). Update on Breast Cancer Susceptibility Genes. In: Senn, HJ., Gelber, R.D., Goldhirsch, A., Thürlimann, B. (eds) Adjuvant Therapy of Primary Breast Cancer VI. Recent Results in Cancer Research, vol 152. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-45769-2_5
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DOI: https://doi.org/10.1007/978-3-642-45769-2_5
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