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 the location of a breast cancer predisposition gene, BRCA1, on chromosome 17q21. Positional cloning pinned it down in 1994. BRCA1 explained some families with very high rates of breast cancer, but only some. Plenty were left with the same inheritance pattern and no explanation. That leftover drove the hunt. It was arithmetic, not a hunch.

What BRCA2 actually does

The name misleads, and it shapes how people hear a test result. BRCA2 is not a cancer gene. It is a repair gene.

DNA breaks constantly, from metabolism, radiation, and copying errors. The worst break cuts both strands of the double helix at once, leaving no intact strand to read from.

NCI describes BRCA1 and BRCA2 as tumor suppressor genes that "play a role in cellular pathways that repair damaged DNA." A Holland-Frei review adds the mechanism: both proteins work with relatives of a yeast protein called Rad51, which repairs double-stranded breaks. All three appear together in one stable complex in the nucleus.

You inherit two copies of BRCA2, one from each parent. One altered copy does not leave you without repair. The working copy carries the load. What you lose is margin. If that working copy is damaged in one cell over a lifetime, that cell loses accurate repair and piles up scrambled DNA. That is why an inherited BRCA2 change raises risk a lot without making cancer certain.

What a BRCA2 result means now

Testing that took a laboratory years in 1995 is now a blood or saliva test. 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. Each child of a carrier has a 50% chance of inheriting it, and it passes through fathers as readily as mothers. That is why families whose history seems to skip the men so often assume the gene is not there when it is.

Note how wide those ranges are. Risk depends on which variant you carry and on the rest of your genetic background. A result gives you a range, not a date.

The part nobody predicted

In 1995 BRCA2 was a risk gene. You could be tested, then choose between closer surveillance and preventive surgery. Knowing changed your options for avoiding cancer. It did nothing for treating one. That changed once the repair function was understood. A tumor cell that has lost its main repair route leans on a backup. Block the backup and the cell cannot handle damage it would otherwise absorb. Normal cells still have a working BRCA2 copy and carry on. NCI calls this synthetic lethality. The drug "does not cause cell death" by itself, but does "in combination with another defect such as the BRCA mutation."

PARP inhibitors were built on that logic. NCI lists four approved for cancers with harmful BRCA1 or BRCA2 changes: olaparib, rucaparib, niraparib, and talazoparib.

So a BRCA2 result today points two ways. It shapes screening and prevention if you have not had cancer. It opens a treatment option if you have. That second use did not exist when the gene was found.

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 probability, not a diagnosis. A negative result in a family with a known variant is reassuring. A negative result in a family nobody has tested means much less.
• 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 referral to ask about here. Bring it up if your family history includes any of these:

• Breast cancer in a relative diagnosed before 50
• Breast and ovarian cancer in one person, or in close relatives on the same side
• More than one relative on the same side with breast, ovarian, prostate, or pancreatic cancer
• Male breast cancer anywhere in the family
• A relative who has already tested positive for a BRCA1 or BRCA2 variant

Symptoms matter regardless of genetics. A new breast lump, skin dimpling, a newly inverted nipple, or bloody nipple discharge needs an appointment now, at any age.

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)
• Holland-Frei Cancer Medicine (NCBI Bookshelf): BRCA1 and BRCA2 Genes (secondary)

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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