The BRCA2 Gene Is Identified (1995)

Historical milestone — this page describes an event dated 1995. It is not current news.

What happened

In its issue of December 21–28, 1995, Nature published "Identification of the breast cancer susceptibility gene BRCA2." Richard Wooster was first author, with Graham Bignell, Jonathan Lancaster and colleagues. The paper reported six different inherited mutations in families with breast cancer, each badly disrupting the reading frame of the same gene. That was the evidence they had found BRCA2 and not a neighboring stretch of DNA.

The same group had mapped the gene to chromosome 13q12–13 the year before, in Science in 1994.

Why there was a second gene to find

In 1990, Hall and colleagues reported in Science that early-onset familial breast cancer was linked to chromosome 17q21, the region that holds BRCA1. NCI's research history says that BRCA2 was identified later, in another gene associated with increased risk of breast and ovarian cancers.

What BRCA2 actually does

The name can mislead. NCI explains that BRCA1 and BRCA2 are genes that produce proteins that help repair damaged DNA, and that they belong to a class called tumor suppressor genes.

Everyone has two copies of each of these genes, one inherited from each parent. People who inherit a harmful change in one of them have a higher risk of certain cancers. It raises risk a lot, but it does not make cancer certain.

What a BRCA2 result means now

NCI says testing may be done with a blood or saliva sample. NCI gives these numbers:

• More than 60% of women who inherit a harmful change in BRCA1 or BRCA2 will develop breast cancer in their lifetime. About 13% of women in the general population will.
• About 13% to 29% of women with a harmful BRCA2 change will develop ovarian cancer, against roughly 1.1% in the general population.
• Between 19% and 61% of men with a harmful BRCA2 change will get prostate cancer by age 80, against about 10.6% in the general population.
• Between 5% and 10% will develop pancreatic cancer, against about 1.7% in the general population.
• Between 1.8% and 7.1% of men with a harmful BRCA2 change will get breast cancer by age 70, against about 0.1% of men in general.

Harmful BRCA changes are uncommon. NCI puts the rate in the general population at about 0.2% to 0.3%, roughly 1 in 400, and higher in some populations, including people of Ashkenazi Jewish descent.

Note how wide those ranges are. They are estimates for groups of people, and they do not give a date or a certainty for any one person.

The part nobody predicted

In 1995 BRCA2 was a risk gene. NCI says cancer cells with harmful changes in BRCA1 or BRCA2 can also be treated with drugs called PARP inhibitors, which block the repair of DNA damage. NCI describes PARP inhibitors as drugs that function by synthetic lethality. Alone, the drug "does not cause cell death" by itself, but does "in combination with another defect such as the BRCA mutation."

NCI lists four PARP inhibitors: olaparib (Lynparza), rucaparib (Rubraca), niraparib (Zejula), and talazoparib (Talzenna). Whether one applies to a particular cancer is a question for that person's care team.

What to keep in perspective

• Most breast cancer is not inherited. NCI's screening summary puts women with inherited risk, BRCA1 and BRCA2 carriers included, at roughly 5% to 10% of breast cancer cases. The rest come from changes acquired during life.
• A positive result is a risk estimate, not a diagnosis.
• What follows a result — screening schedules, risk-reducing surgery, medication — belongs in a conversation with a genetic counselor and a clinician.

When to get checked

Genetic counseling, not a symptom, is the usual first step to ask about here. NCI says a risk assessment before testing reviews factors that make it more likely that someone inherited a harmful BRCA change. These include:

• A family member with an inherited harmful change in BRCA1 or BRCA2
• Ashkenazi Jewish heritage
• A personal or family history of breast cancer at age 50 or younger
• A personal or family history of ovarian cancer, male breast cancer, pancreatic cancer, or metastatic or high-risk prostate cancer

Symptoms matter whatever the genetics. Call your care team about a new breast lump, skin dimpling, a newly inverted nipple, or bloody nipple discharge. If symptoms are severe or come on suddenly, call 911 or go to an emergency room.

Sources

This article was written from the sources below, which were checked on the source-check date shown above.

• Wooster R, Bignell G, Lancaster J, et al. Identification of the breast cancer susceptibility gene BRCA2. Nature. 1995 Dec 21-28;378(6559):789-92 (PMID 8524414) (primary)
• Wooster R, Neuhausen SL, Mangion J, et al. Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science. 1994;265:2088-90 (PMID 8091231) (primary)
• NCI PDQ: Breast Cancer Screening (Health Professional Version) (official)
• NCI: BRCA Gene Changes — Cancer Risk and Genetic Testing (official)
• NCI Research Progress: Discovery — BRCA Connection to Breast and Ovarian Cancer (official)

How this article was prepared

An AI-assisted editorial system helped prepare this page. No named medical reviewer has reviewed it unless one is listed.

The National Cancer Information Foundation publishes Cancer Explained. This page is for learning. It is not medical advice and does not suggest a test or treatment.

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