Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer

Michael Krainer, Sandra Silva-Arrieta, Michael G. FitzGerald, Akira Shimada, Chikashi Ishioka, Ryunosuke Kanamaru, Deborah J. MacDonald, Hilal Unsal, Dianne M. Finkelstein, Anne Bowcock, Kurt J. Isselbacher, Daniel A. Haber

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Abstract

Background: Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to breast cancer. BRCA1 mutations are found in approximately 12 percent of women with breast cancer of early onset, and the specific mutation causing a deletion of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi Jewish population, contributes to 21 percent of breast cancers among young Jewish women. The contribution of BRCA2 mutations to breast cancer of early onset is unknown. Methods: Lymphocyte specimens from 73 women with breast cancer diagnosed by the age of 32 were studied for heterozygous mutations of BRCA2 by a complementary-DNA-based protein- truncation assay, followed by automated nucleotide sequencing. In addition, specimens from 39 Jewish women with breast cancer diagnosed by the age of 40 were tested for specific mutations by an allele-specific polymerase chain reaction. Results: Definite BRCA2 mutations were found in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated with fewer cases than BRCA1 (P = 0.03). The specific BRCA2 mutation causing a deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi Jewish population, was observed in 1 of the 39 young Jewish women with breast cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent), indicating that it has a small role as a risk factor for early-onset breast cancer. Among young women with breast cancer, there are BRCA2 mutations that cause truncation of the extreme C terminus of the protein and that may be functionally silent, along with definite truncating mutations. Conclusions: Germ-line mutations in BRCA2 contribute to fewer cases of breast cancer among young women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller increase in the risk of early-onset breast cancer.

Original languageEnglish
Pages (from-to)1416-1421
Number of pages6
JournalNew England Journal of Medicine
Volume336
Issue number20
DOIs
Publication statusPublished - 1997
Externally publishedYes

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Breast Neoplasms
Mutation
Germ-Line Mutation
BRCA2 Gene
Confidence Intervals
BRCA1 Gene
Thymine
Guanine
Adenine
Protein C
Population
Nucleotides
Complementary DNA
Alleles
Lymphocytes
Polymerase Chain Reaction

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Krainer, M., Silva-Arrieta, S., FitzGerald, M. G., Shimada, A., Ishioka, C., Kanamaru, R., ... Haber, D. A. (1997). Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. New England Journal of Medicine, 336(20), 1416-1421. https://doi.org/10.1056/NEJM199705153362003

Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. / Krainer, Michael; Silva-Arrieta, Sandra; FitzGerald, Michael G.; Shimada, Akira; Ishioka, Chikashi; Kanamaru, Ryunosuke; MacDonald, Deborah J.; Unsal, Hilal; Finkelstein, Dianne M.; Bowcock, Anne; Isselbacher, Kurt J.; Haber, Daniel A.

In: New England Journal of Medicine, Vol. 336, No. 20, 1997, p. 1416-1421.

Research output: Contribution to journalArticle

Krainer, M, Silva-Arrieta, S, FitzGerald, MG, Shimada, A, Ishioka, C, Kanamaru, R, MacDonald, DJ, Unsal, H, Finkelstein, DM, Bowcock, A, Isselbacher, KJ & Haber, DA 1997, 'Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer', New England Journal of Medicine, vol. 336, no. 20, pp. 1416-1421. https://doi.org/10.1056/NEJM199705153362003
Krainer, Michael ; Silva-Arrieta, Sandra ; FitzGerald, Michael G. ; Shimada, Akira ; Ishioka, Chikashi ; Kanamaru, Ryunosuke ; MacDonald, Deborah J. ; Unsal, Hilal ; Finkelstein, Dianne M. ; Bowcock, Anne ; Isselbacher, Kurt J. ; Haber, Daniel A. / Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer. In: New England Journal of Medicine. 1997 ; Vol. 336, No. 20. pp. 1416-1421.
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title = "Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer",
abstract = "Background: Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to breast cancer. BRCA1 mutations are found in approximately 12 percent of women with breast cancer of early onset, and the specific mutation causing a deletion of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi Jewish population, contributes to 21 percent of breast cancers among young Jewish women. The contribution of BRCA2 mutations to breast cancer of early onset is unknown. Methods: Lymphocyte specimens from 73 women with breast cancer diagnosed by the age of 32 were studied for heterozygous mutations of BRCA2 by a complementary-DNA-based protein- truncation assay, followed by automated nucleotide sequencing. In addition, specimens from 39 Jewish women with breast cancer diagnosed by the age of 40 were tested for specific mutations by an allele-specific polymerase chain reaction. Results: Definite BRCA2 mutations were found in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated with fewer cases than BRCA1 (P = 0.03). The specific BRCA2 mutation causing a deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi Jewish population, was observed in 1 of the 39 young Jewish women with breast cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent), indicating that it has a small role as a risk factor for early-onset breast cancer. Among young women with breast cancer, there are BRCA2 mutations that cause truncation of the extreme C terminus of the protein and that may be functionally silent, along with definite truncating mutations. Conclusions: Germ-line mutations in BRCA2 contribute to fewer cases of breast cancer among young women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller increase in the risk of early-onset breast cancer.",
author = "Michael Krainer and Sandra Silva-Arrieta and FitzGerald, {Michael G.} and Akira Shimada and Chikashi Ishioka and Ryunosuke Kanamaru and MacDonald, {Deborah J.} and Hilal Unsal and Finkelstein, {Dianne M.} and Anne Bowcock and Isselbacher, {Kurt J.} and Haber, {Daniel A.}",
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T1 - Differential contributions of BRCA1 and BRCA2 to early-onset breast cancer

AU - Krainer, Michael

AU - Silva-Arrieta, Sandra

AU - FitzGerald, Michael G.

AU - Shimada, Akira

AU - Ishioka, Chikashi

AU - Kanamaru, Ryunosuke

AU - MacDonald, Deborah J.

AU - Unsal, Hilal

AU - Finkelstein, Dianne M.

AU - Bowcock, Anne

AU - Isselbacher, Kurt J.

AU - Haber, Daniel A.

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N2 - Background: Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to breast cancer. BRCA1 mutations are found in approximately 12 percent of women with breast cancer of early onset, and the specific mutation causing a deletion of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi Jewish population, contributes to 21 percent of breast cancers among young Jewish women. The contribution of BRCA2 mutations to breast cancer of early onset is unknown. Methods: Lymphocyte specimens from 73 women with breast cancer diagnosed by the age of 32 were studied for heterozygous mutations of BRCA2 by a complementary-DNA-based protein- truncation assay, followed by automated nucleotide sequencing. In addition, specimens from 39 Jewish women with breast cancer diagnosed by the age of 40 were tested for specific mutations by an allele-specific polymerase chain reaction. Results: Definite BRCA2 mutations were found in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated with fewer cases than BRCA1 (P = 0.03). The specific BRCA2 mutation causing a deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi Jewish population, was observed in 1 of the 39 young Jewish women with breast cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent), indicating that it has a small role as a risk factor for early-onset breast cancer. Among young women with breast cancer, there are BRCA2 mutations that cause truncation of the extreme C terminus of the protein and that may be functionally silent, along with definite truncating mutations. Conclusions: Germ-line mutations in BRCA2 contribute to fewer cases of breast cancer among young women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller increase in the risk of early-onset breast cancer.

AB - Background: Germ-line mutations in the BRCA1 and BRCA2 genes predispose women to breast cancer. BRCA1 mutations are found in approximately 12 percent of women with breast cancer of early onset, and the specific mutation causing a deletion of adenine and guanine (185delAG), which is present in 1 percent of the Ashkenazi Jewish population, contributes to 21 percent of breast cancers among young Jewish women. The contribution of BRCA2 mutations to breast cancer of early onset is unknown. Methods: Lymphocyte specimens from 73 women with breast cancer diagnosed by the age of 32 were studied for heterozygous mutations of BRCA2 by a complementary-DNA-based protein- truncation assay, followed by automated nucleotide sequencing. In addition, specimens from 39 Jewish women with breast cancer diagnosed by the age of 40 were tested for specific mutations by an allele-specific polymerase chain reaction. Results: Definite BRCA2 mutations were found in 2 of the 73 women with early-onset breast cancer (2.7 percent; 95 percent confidence interval, 0.4 to 9.6 percent), suggesting that BRCA2 is associated with fewer cases than BRCA1 (P = 0.03). The specific BRCA2 mutation causing a deletion of thymine (6174delT), which is found in 1.3 percent of the Ashkenazi Jewish population, was observed in 1 of the 39 young Jewish women with breast cancer (2.6 percent; 95 percent confidence interval, 0.09 to 13.5 percent), indicating that it has a small role as a risk factor for early-onset breast cancer. Among young women with breast cancer, there are BRCA2 mutations that cause truncation of the extreme C terminus of the protein and that may be functionally silent, along with definite truncating mutations. Conclusions: Germ-line mutations in BRCA2 contribute to fewer cases of breast cancer among young women than do mutations in BRCA1. Carriers of BRCA2 mutations may have a smaller increase in the risk of early-onset breast cancer.

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