Discovery of Breast Cancer Genes Summary

  • Last updated on November 10, 2022

Inherited forms of breast cancer account for approximately 10 percent of cases. Researchers identified two genes, BRCA1 and BRCA2, which were mutations that were associated with inherited forms of the disease. Identification of these genes allowed for a method of screening women who were at a particular risk of developing the disease prior to middle age.

Summary of Event

As is true for most forms of cancer, the risk among women of developing breast cancer increases significantly with age. While the risk is approximately one in ninety-three among women under the age of forty-five, the risk increases to about one in ten among women over the age of eighty. The overall risk during a woman’s lifetime is approximately one in eight, with some 200,000 cases diagnosed each year. While some behaviors, such as high-fat diets and estrogen replacement therapy, may increase the risk, in most cases the underlying cause of breast cancer is unknown. It should be noted that no evidence exists that undergoing an abortion increases the risk of developing cancer. Cancer;genetics Genetics;breast cancer Breast cancer genes Diseases;cancers BRCA genes [kw]Discovery of Breast Cancer Genes (1990-1994) [kw]Breast Cancer Genes, Discovery of (1990-1994) [kw]Cancer Genes, Discovery of Breast (1990-1994) [kw]Genes, Discovery of Breast Cancer (1990-1994) Cancer;genetics Genetics;breast cancer Breast cancer genes Diseases;cancers BRCA genes [g]North America;1990-1994: Discovery of Breast Cancer Genes[07580] [g]United States;1990-1994: Discovery of Breast Cancer Genes[07580] [c]Biology;1990-1994: Discovery of Breast Cancer Genes[07580] [c]Health and medicine;1990-1994: Discovery of Breast Cancer Genes[07580] [c]Genetics;1990-1994: Discovery of Breast Cancer Genes[07580] [c]Science and technology;1990-1994: Discovery of Breast Cancer Genes[07580] King, Mary-Claire Skolnick, Mark Stratton, Michael

The first suggestion that breast cancer might have a genetic basis was put forward by French surgeon Pierre Paul Broca, Broca, Pierre Paul who noted that thirty-eight members of his wife’s family, spanning several generations, had developed cancer. In the 1930’s and 1940’s, several researchers noted the increased frequency of breast cancer in certain families; many of those cases involved younger women.

During the 1970’s, several developments pointed to the molecular basis for many forms of cancer. The first development was the discovery of proto-oncogenes, genes that produced proteins that regulated the movement of cells through a cycle that included cell division. Most of these gene products fell into certain categories: growth factors that induced cell division, receptors that responded to the presence of these factors, signaling mechanisms within the cell, and suppressor proteins that monitored the overall process. The correct combinations of mutations in these genes could result in uncontrolled cell division, a cancer.

Equally important during these years was the development of techniques that could isolate and analyze specific genes, including those associated with cell regulation and cancer. Once a gene was identified, it became possible both to locate the site of that gene using known genetic “markers” on the chromosome, and to sequence the nucleotides of which it was composed.

During the early 1980’s, Mary-Claire King, a geneticist and molecular biologist on the faculty of the University of California, Berkeley, began her own study of the frequency of breast cancer in some families. Participating in a study carried out by the National Cancer Institute called the Surveillance, Epidemiology and End Result (SEER) Program, King and her coworkers noted an increased risk of breast cancer in younger women if members of their families had developed the disease early. Some of these women had an 85 percent or greater chance of developing the disease, pointing to a specific genetic cause. King calculated that at least one in eight hundred women carried the gene. Women of Ashkenazi (Eastern European) Jewish ancestry had an even greater frequency: one in one hundred. Analysis of the pattern of cancer in these families indicated that, in all likelihood, only a single gene was associated with increased risk.

Over a period of three years, King and her colleagues tested several hundred genetic probes while searching for the location of the “breast cancer gene,” eventually locating it in a region of some one thousand genes on chromosome 17, a discovery which she reported in 1990. Further research by Mark Skolnick at the University of Utah resulted in identification of the precise location of the gene, which was called BRCA1. Earlier in his scientific career, Skolnick had been involved in identification of gene locations by utilizing known genetic probes and markers. Techniques he used to locate BRCA1 had earlier been utilized in identifying the location of another cancer gene, one for familial melanoma. The location of BRCA1 was published in the journal Science in 1994.

If indeed this breast cancer gene was associated with inherited forms of the disease, then the same gene should be present in women at mathematically significant risk for the disease—women whose close relatives developed the disease at age forty-five or younger. Genetic testing of these women confirmed the presence of the gene. The same genetic mutations were later shown to be associated with inherited forms of ovarian cancer.

The breast cancer gene identified by King accounted for 90 percent of inherited forms of breast cancer, suggesting another gene may also exist. Likewise, mutations in BRCA1 did not account for inherited forms of breast cancer in men. In 1994, Skolnick and Michael Stratton, the latter working in London, reported the identification of a second gene, called BRCA2. This gene accounted for nearly all of the remaining forms of inherited breast cancer and also accounted for the disease in men. Identification of the gene was, in part, fortuitous; one of the families studied by Skolnick demonstrated particular markers near a breast cancer gene on chromosome 13. The gene was later located at a specific site on chromosome 13, which the teams reported in December of 1994.

Identification of the genes led to questions about their specific functions. BRCA1 encodes a protein of approximately nineteen hundred amino acids, whereas BRCA2 encodes a protein of approximately thirty-five hundred amino acids. The precise function of each of these proteins, the roles they play in regulating the cell, remains ambiguous. Evidence indicates that they play several roles in regulating the cell, including DNA repair, regulation of cell division, and regulation of gene expression.

It also became apparent that any association of these genes with inherited forms of cancer is dependent on the precise location of the error. Mutations at certain positions in the BRCA proteins have limited effects, while other mutations are directly associated with an increased risk for the disease. The molecular basis for the different effects associated with these mutations remains to be discerned.


Despite advances in research and treatment in recent years, breast cancer remains the most common form of non-smoking-related cancer in women. Approximately 10 percent of the more than 200,000 cases diagnosed each year have a genetic basis. Earlier diagnosis significantly improves the prognosis once the disease develops; the ability to screen women at significant risk for the disease plays a significant role in being able to monitor the disease in its earliest stages.

A woman with a mutation in the BRCA1 gene has been estimated as having an 85 percent chance of developing the disease during her lifetime. The risk varies significantly, however, depending upon where the specific mutation is located in the gene; the actual risk may be lower, or greater, given its location. Mutations in BRCA2 play a similar, if less frequent, role.

The ability to screen for the mutations may also serve to eliminate the fear of cancer. A woman with a close family member diagnosed with cancer may decide to undergo a preventive mastectomy rather than risk the disease. Screening may also indicate the absence of the mutations.

Significant questions remain as to the role of the BRCA1 and BRCA2 genes in tumor formation. Why, for example, do mutations in these genes contribute to breast or ovarian cancer, but not cancer involving other tissues? Do these genes play any role in the development of other forms of breast cancer, either in contributing or preventing the disease? A greater understanding of the variety of functions attributed to the gene products of BRCA1 and BRCA2 may lend itself to better understanding of the regulation of cell activities in general. Cancer;genetics Genetics;breast cancer Breast cancer genes Diseases;cancers BRCA genes

Further Reading
  • citation-type="booksimple"

    xlink:type="simple">Adler, Richard. “Breast Cancer Genes.” In Magill’s Survey of Science: Life Science. Supplement, edited by Frank Magill. Pasadena, Calif.: Salem Press, 1998. Presents a summary of the research that led to the discovery of the breast cancer genes.
  • citation-type="booksimple"

    xlink:type="simple">Davies, Kevin, and Michael White. Breakthrough: The Race to Find the Breast Cancer Gene. New York: John Wiley & Sons, 1996. Popular account of the research behind identification of genes associated with inherited forms of breast cancer.
  • citation-type="booksimple"

    xlink:type="simple">McKinnell, Robert, et al. The Biological Basis for Cancer. New York: Cambridge University Press, 2006. Examines the genetic basis for many forms of cancer, including the role of BRCA genes in breast cancer.
  • citation-type="booksimple"

    xlink:type="simple">Maclachlan, Timothy, and Wafik El-Deiry. “Pointing (Zinc) Fingers at BRCA1 Targets.” Nature Medicine 6 (December, 2000): 1318-1319. Discusses the function of the gene product in regulating DNA repair. An explanation of the importance of the primary breast cancer gene.
  • citation-type="booksimple"

    xlink:type="simple">Turkington, Carol, et al. Encyclopedia of Breast Cancer. New York: Facts On File, 2004. Provides definitions of primary terms and addresses topics relevant to breast cancer. Directed toward a general audience.
  • citation-type="booksimple"

    xlink:type="simple">Wooster, Richard, et al. “Identification of the Breast Cancer Susceptibility Gene BRCA2.” Nature 378 (December 21, 1995): 789-792. Intended for readers with some knowledge of genetic science. Describes the identification and localization of the BRCA2 gene.

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