Mary-Claire King maps BRCA1 to chromosome 17

Historical milestone — this page describes an event dated 1990. It is not current breaking news.

The paper

On 21 December 1990, Science published "Linkage of early-onset familial breast cancer to chromosome 17q21". The authors were Jeff Hall, Ming Lee, Beth Newman, Jan Morrow, Lee Anne Anderson, Bo Huey and Mary-Claire King, working at the School of Public Health at the University of California, Berkeley.

The abstract begins with a caution that still holds. Breast cancer is usually caused by genetic changes in the breast's own cells during life. Only occasionally is susceptibility inherited.

What the paper reported was a location. Chromosome 17q21 appeared to hold a gene for inherited susceptibility in families where breast cancer struck young.

How you find a gene without seeing it

There was no way to read a whole human genome in 1990. The method was linkage analysis, and it works by association rather than by looking.

Scientists track harmless, variable markers scattered along the chromosomes through large families. If one marker is inherited by the family members who develop the disease, and not by those who do not, the gene causing the disease is probably sitting near that marker. Chromosomes shuffle at each generation, but stretches close together tend to travel as a unit.

Strength of evidence is expressed as a lod score, the logarithm of the odds favoring linkage. A lod score of 3 is the conventional threshold, meaning 1,000-to-1 odds.

King's group reported a lod score of 5.98 for linkage between breast cancer susceptibility and a marker called D17S74 in early-onset families. That is odds of roughly a million to one.

The negative result did as much work as the positive one

In families where breast cancer appeared later in life, the lod scores were negative. The link was absent.

That split told the field something important: inherited breast cancer is not one thing. The paper reported likelihood ratios favoring heterogeneity among families ranging from 2,000 to 1 to more than a million to one. Different families carried different causes.

That finding is why the search continued after 1990 rather than stopping. It pointed directly at the existence of other genes, and BRCA2 was mapped a few years later.

Four more years to the gene itself

Mapping is not identification. The 1990 paper narrowed the search to a region of a chromosome containing many genes.

In October 1994, Science published "A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1" from Yoshio Miki and colleagues, based at the University of Utah Medical Center. They found probable disease-causing mutations in five of eight families thought to carry BRCA1. The mutations included an 11-base-pair deletion, a single-base insertion, a stop codon and a missense change.

The gene encodes a protein of 1,863 amino acids, expressed in many tissues including breast and ovary. The authors wrote that identifying it should help with early diagnosis of susceptibility in some people.

Four years separated the map from the gene. That gap is the ordinary shape of this kind of science.

What it means for a person today

A harmful inherited change in BRCA1 or BRCA2 raises risk substantially, and NCI puts numbers on it.

More than 60% of women who inherit a harmful BRCA1 or BRCA2 change will develop breast cancer during their lifetime, against about 13% of women in general. For ovarian cancer it is about 39% to 58% with BRCA1 and about 13% to 29% with BRCA2, against about 1.1% in general.

The mechanism explains the pattern. BRCA1 and BRCA2 repair DNA. A carrier inherits one working copy and one faulty copy, and the working copy is usually enough. If that second copy is damaged during life, the cell loses a repair route and can become cancer.

That same weakness is now exploited as a treatment. PARP inhibitors block a different repair route, and cells lacking BRCA function cannot cope with losing both. Our page on breast cancer covers where these drugs fit.

When to get checked

Two separate things follow from this history: routine screening, and testing for inherited risk.

For screening, the US Preventive Services Task Force recommends mammography every two years for women aged 40 to 74. It found the evidence insufficient to judge screening at 75 or older, and insufficient to judge added ultrasound or MRI for women with dense breasts.

For inherited risk, our page on genetic testing for cancer risk covers what a panel test reads. NCI lists the family patterns worth raising with a doctor or genetic counselor:

• Breast cancer diagnosed young, or in several close relatives.
• Breast and ovarian cancer in the same family line.
• Cancer in both breasts.
• Breast cancer in a man.
• Ovarian, pancreatic or metastatic prostate cancer in a close relative.
• A relative already known to carry a harmful gene change.

Testing is generally recommended for anyone diagnosed with triple-negative breast cancer, ovarian cancer, pancreatic cancer, male breast cancer, metastatic prostate cancer, or colorectal cancer before age 50.

Where breast cancer stands now

The American Cancer Society estimates about 321,910 new female breast cancers in the United States in 2026 and about 42,140 deaths, a projection published on SEER's stat page. Five-year relative survival for 2016 to 2022 was 91.9%, and the median age at diagnosis is 64.

Stage drives the range, over the same 2016 to 2022 diagnoses: 100.0% five-year relative survival for localized disease, 87.5% for regional spread, and 33.8% once distant. Localized disease accounts for 64% of diagnoses. About 13.0% of women are diagnosed with breast cancer at some point in life. These are population figures and describe no individual.

What this does not mean

The 1990 paper did not identify BRCA1. It located a region, and other laboratories found the gene four years later.

It does not describe most breast cancer. Inherited changes account for a minority of cases, and the paper itself says so in its first sentence.

And carrying a BRCA change is a risk figure, not a diagnosis. A large share of carriers never develop the cancers in question, which is why the conversation belongs with a genetic counselor rather than a search engine.

Sources

• Science 1990, Linkage of early-onset familial breast cancer to chromosome 17q21, PMID 2270482 — https://pubmed.ncbi.nlm.nih.gov/2270482/
• Science 1994, A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1, PMID 7545954 — https://pubmed.ncbi.nlm.nih.gov/7545954/
• NCI, BRCA Gene Changes: Cancer Risk and Genetic Testing — https://www.cancer.gov/about-cancer/causes-prevention/genetics/brca-fact-sheet
• NCI, Genetic Testing for Inherited Cancer Risk — https://www.cancer.gov/about-cancer/causes-prevention/genetics/genetic-testing-fact-sheet
• US Preventive Services Task Force, Breast Cancer: Screening — https://www.uspreventiveservicestaskforce.org/uspstf/recommendation/breast-cancer-screening
• SEER Cancer Stat Facts, Female Breast Cancer — https://seer.cancer.gov/statfacts/html/breast.html

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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