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Paul Broca

The Cancer Gene More Men Should Test For

The Atlantic

www.theatlantic.com › health › archive › 2024 › 11 › brca-breast-cancer-men-prostate-pancreas › 680698

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When Mary-Claire King discovered the first gene linked to hereditary breast cancer in 1990, she also got to decide its name. She settled on the four letters BRCA, which had three distinct meanings. The name paid homage to UC Berkeley, where King worked at the time; more to the point, it was a nod to Paul Broca, the 19th-century French physician whose work established a link between family history and breast cancer. It was also an abbreviation for breast cancer.

A few years after King discovered BRCA1, a second BRCA gene, BRCA2, was identified. Together, they now have more name recognition than probably any other gene, their profile boosted by research that has shown staggering effects on cancer risk. Awareness campaigns followed. A 2013 New York Times op-ed in which Angelina Jolie revealed she’d had a preventive double mastectomy because of her own BRCA mutation drove many women to seek DNA tests themselves. The BRCA genes became inextricably linked with breasts, as much as the pink ribbons that have become an international symbol of breast cancer. And in driving more women to find out if they have BRCA mutations, it’s helped to greatly reduce the risk of hereditary breast cancer.

But in the three decades since the genes were discovered, scientists have learned that BRCA mutations can also lead to cancer in the ovaries, the pancreas, and the prostate. More recently, they have been linked with cancers in other parts of the body, such as the esophagus, stomach, and skin. As many as 60 percent of men with changes in BRCA2 develop prostate cancer, yet men are generally far less aware than women that BRCA mutations can affect them at all.

“It’s a branding problem,” Colin Pritchard, a professor of laboratory medicine and pathology at the University of Washington, told me. Men with family histories of breast cancer may not realize that they should get screened. Physicians, too, lack awareness of which men should get tested, and what steps to take when a mutation is found. Now Pritchard and other researchers are working to rebrand BRCA and the syndrome associated with it so that more men and their doctors consider testing.

Normally, the BRCA genes produce proteins that help repair damaged DNA throughout the body. Most people who carry mutations that impair the gene’s function are diagnosed with hereditary breast and ovarian cancer syndrome. (Having HBOC means a person is at increased risk for cancer, not that they already have an illness.) Most breast-cancer cases have no known hereditary link, but more than 60 percent of women with a harmful BRCA1 or BRCA2 mutation will develop breast cancer, compared with about 13 percent of the wider female population. Men, of course, can get breast cancer too, but it's rare, even among BRCA-mutation carriers.

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The full significance of the link between BRCA mutations and pancreatic and prostate cancer has become clear only recently—perhaps in the past decade, said Pritchard. The exact risk these mutations impart to men varies widely in studies. But it’s clearly significant: Not only are men with BRCA mutations more likely to develop prostate cancer, they are also more likely to develop the more aggressive forms of the disease.

Roughly one in 400 people carry a harmful mutation in BRCA1 or BRCA2, and half of them are men. But women are far more likely to have been tested for the mutations—up to 10 times as likely, according to one study. “Beyoncé’s dad was the only man that I had ever heard of who had it,” Christian Anderson, a 46-year-old social-sciences professor in Washington State who carries a BRCA2 mutation, told me. Anderson got tested after his sister was diagnosed with breast cancer, but countless men like him go undetected. Only about half of Americans get an annual physical, and doctors aren’t always aware of BRCA-screening recommendations for men. Many men who do test for a BRCA mutation report doing it for their daughters, and studies have shown that they tend to be confused about their risks of developing cancer themselves.

BRCA-awareness campaigns have led many women to get tested; in the two weeks after Angelina Jolie’s viral op-ed, researchers found that BRCA-testing rates went up by 65 percent. In that case, more people may gotten tested than needed to, but in general, the rise in cancer screenings and elective surgical interventions have helped reduce the rates of deaths from breast and ovarian cancers. Education about the genes’ links to other cancers could do the same for men. To that end, Pritchard argued in a 2019 Nature commentary that Hereditary Breast and Ovarian Cancer syndrome should be renamed King Syndrome after Mary-Claire King. “We need to really rethink this if we're going to educate the public about the importance of these genes for cancer risk for everyone, not just women,” he told me.

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As understanding of BRCA’s risks for men has grown, Pritchard’s idea has started to catch on. King, who is now a professor of genome sciences and medicine at the University of Washington, demurred when I asked her whether the syndrome associated with the BRCA genes should be renamed after her, but agreed that awareness campaigns have focused too narrowly on breasts and ovaries. “We need to bring this awareness to men in the same way that we have for 30 years now to women,” she told me.

How exactly Pritchard’s plan might be put into action is unclear. Gene names are overseen by an international committee and rarely changed. That’s part of why Pritchard is suggesting that the name of the syndrome associated with BRCA mutations become King Syndrome—no single governing body oversees that. Recently, ClinGen, an international group of researchers that works to parse the medical significance of genes, recommended that HBOC be rechristened BRCA-related cancer predisposition. (Pritchard told me he thinks that name isn’t quite as “catchy” as King Syndrome.)

Uncoupling the syndrome associated with BRCA mutations from breasts would likely be only the first step in getting more at-risk men screened for cancer. It would also be an important step in understanding the full impact of BRCA mutations on men. Because fewer men than women have been tested for BRCA mutations, scientists still don’t have a complete picture of their risk. For example, Pritchard told me, it’s only as more attention has been drawn to male BRCA risk that researchers have discovered mutations are linked to especially aggressive forms of prostate cancer. Penn Medicine recently launched a program dedicated to men and BRCA in part to continue this sort of research.

[Read: Scientists have been studying cancers in a very strange way for decades]

BRCA’s name is a legacy of a time when scientists thought genetics would offer a simple way to diagnose and treat disease—that one specific mutation would point definitively to one specific cancer. But today, “the idea that a gene would only affect one type of cancer risk is probably outmoded,” Pritchard said. The more scientists explore the human genome, the more complex its connections to health appear. It turns out that when genes don’t work like they should, the possible consequences may very well be infinite.