Utah is a veritable wellspring of genetic discoveries. Researchers at the University of Utah (U of U) can claim the discovery of 50 genes involved in inherited disease risk.

The foundation of that wellspring was a singular resource: an abundance of detailed family trees. But it took the foresight of several Utah researchers to understand the potential of this data and determine how to harness its power for genetic discovery.

This focus on a genetic approach to understanding disease came to the attention of Jon M. and Karen Huntsman. Jon Huntsman lost his mother to cancer. After his own experience with the disease, he and Karen became committed to the cancer cause. When they learned of the genetics work occurring at the U of U—in their own backyard—they felt their financial support would have the greatest impact there. In 1995, the Huntsman family made a major gift that enabled the establishment of a state-of-the-art research, education, and cancer care facility on the U of U campus, becoming critical investors in the cancer genetics work that has had a significant impact across the world. Today Huntsman Cancer Institute has grown into more than one million square feet of research and clinical space.

And Utah’s researchers—many of whom joined Huntsman Cancer Institute when it was founded in 1995—made critical contributions to these cancer genetics discoveries. These discoveries include the identification of genes associated with hereditary breast, ovarian, colon, head and neck cancers, multiple myeloma, and melanoma.

“A confluence of the perfect environment with the perfect people happened here in Utah,” says Lisa Cannon-Albright, PhD, a genetic epidemiologist at Huntsman Cancer Institute and leader of the Genetic Epidemiology Program at the U of U. “So many people in Utah had vision.”

That vision started in the mid–twentieth century, when researchers began recognizing how the state’s unique assets could aid in studying inherited disease.

“Utah is particularly well adapted for the study of human genetics because the families are large—larger, I think, than you would find generally in the population,” said U of U researchers Frank H. Tyler, MD, and Fayette E. Stephens, PhD, in a 1954 publication titled Methods of Investigation of Human Inheritance.

Not only that, Tyler and Stephens noted, but the state’s residents had such an interest in genealogy that they “spend much time and money looking up their family records.” Indeed, long before genealogy became a national hobby, Utahns were tracing their family lines, recording information about generation upon generation of relatives.

In the 1940s and ’50s, Tyler and Stephens, along with Maxwell Wintrobe, MD, PhD, availed themselves of those extensive pedigrees to study a potential inherited predisposition to muscular dystrophy. The National Institutes of Health awarded its first-ever external research grant to Wintrobe for this research. Around the same time, Charles Woolf and Eldon Gardner from the Laboratory of Human Genetics at the U of U identified likely inherited susceptibilities to breast cancer and colon cancer through studying pedigrees.

But there were limitations. Researchers looking for cancer incidence in relatives who had died or were otherwise unavailable for interview had to rely on the accounts of other family members, a sort of medical hearsay without medical records for corroboration—which was often the case.

Salt Lake City surgical oncologist Charles Smart, MD, recognized the need for a credible, complete source of cancer incidence data. In 1966, Smart founded the Utah Cancer Registry to record all cancer diagnoses in the state. One of the first state cancer registries in the nation, the Utah Cancer Registry became one of the original members of the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program.

The next leap forward came in the 1970s. U of U researchers, including Mark Skolnick, PhD, assembled a rich repository of Utah family trees, joining these to form a vast genealogical database. Skolnick and his team received books of Utah genealogies. The team copied and computerized records of some 170,000 families that had ties to Utah.

The goal was to link this genealogical data with the cancer registry. And when that happened, it became the critical resource University of Utah researchers needed to better define and understand the heritable nature of cancer. The Utah Genealogy Resource, now known as the Utah Population Database (UPDB), led to a succession of pivotal genetics discoveries.

“Once you had those records linked, you could look in an unbiased way across the population of most of the state and identify pedigrees that had an excess of a certain type of cancer,” explains Sean Tavtigian, PhD, director of the Center for Cancer Genetics at Huntsman Cancer Institute. The 1990s saw breakthrough after breakthrough, beginning in the first year of that decade with the characterization of the neurofibromatosis type 1 (NF1) gene.

Around the same time, a group of scientists at a University of Utah-sponsored retreat at Alta Ski Resort had a conversation that spurred a new view of how to create a genetic linkage map of the human genome. This meeting included Ray White, PhD, who would go on to be named founding director of Huntsman Cancer Institute in 1995. The scientists proposed the use of what they later called restriction fragment polymorphisms (RFLPs) to identify disease-causing genes.

In 1991, White and other researchers used genealogical data to identify a mutation of the APC gene. Carriers of the mutated gene have a nearly 100% chance of developing colon cancer in their lifetime. Later teams used the UPDB to trace a specific APC mutation all the way back to a Pilgrim couple who arrived on America’s shores in the 1630s.

These individuals and many others contributed to several gene discoveries. The key to the work was the unparalleled collaboration across many groups: medical doctors who prioritized research in their clinical practice; cancer patients who agreed to share data for research studies; and research scientists who analyzed data and published findings. Among the discoveries included the identification of p16 as a susceptibility gene for melanoma in 1993. Tavtigian had been hired that year as a postdoc at Myriad Genetics, a small startup then and a biotechnology giant now.

“When I started, Myriad was a company of about 10 people. I think I was employee number 10,” Tavtigian says.

Skolnick, along with Peter Meldrum, founded Myriad to aid in identifying the location of the breast and ovarian cancer susceptibility gene BRCA1. Four years earlier, a laboratory at University of California, Berkeley, led by Mary-Claire King, PhD, had found evidence for a possible hereditary breast cancer gene located somewhere on human chromosome 17 that she named BReast CAncer Gene 1, or BRCA1. This led to researchers around the world engaged in a race to find the specific location of this gene. It was the Utah team led by Skolnick who found the precise location of the gene in 1994. One secret to their success included the use of bacterial artificial chromosomes (BACs), a highly accurate cloning technology. The other secret: access to multiple Utah genealogies in the database where there was a strong family history of these diseases. With every family they studied, the researchers narrowed down the location more and more.

In 1996, Tavtigian led the team that did the complete cloning of BRCA2, followed by the cloning of PTEN a few years later. PTEN mutations raise the risk for cancers including glioma, prostate, breast, and kidney.

“We had a really successful streak,” Tavtigian says. “It was a really exciting time because we knew we were making important discoveries. We knew that in the long run, the results were going to be adding a lot of years to patients’ lives.”

Huntsman Cancer Institute medical oncologist Saundra Buys, MD, is among the physicians who were critical in championing the translation of genetics research to the clinic to benefit patients and families. She says patients with an extensive family history of cancer are foundational to any research discoveries made. The teams who worked on these discoveries credit the Utah families who actively and generously participated in the research as the key to their success.

Today, Buys cares for patients in Huntsman Cancer Institute’s Family Cancer Assessment Clinic. Here, Buys and colleagues work with people with a family history of cancer. They review medical records, and, if appropriate, recommend genetic testing for mutations in families with a high incidence of cancer. The clinic also provides genetic counseling to tell affected family members what it means to carry a predisposition gene, and whether they need specific interventions, like earlier or more frequent cancer screenings.

For high-risk individuals, earlier screenings are crucial to detect cancer early if it does occur, says Buys. “When you detect cancer early, it’s much more likely to be curable and it’s more likely to be cured with less aggressive treatments.”

With the introduction of new resources and initiatives, Huntsman Cancer Institute has had a steady tempo of major investments to build upon Utah’s history of genetic discovery. In 2011, researchers led by Geri Mineau, PhD, completed what they called the Master Linkage Project. This work linked the electronic medical records of 3.4 million individuals to the UPDB, resulting in a major advance in infrastructure for population research. Also, Huntsman Cancer Institute created the Center for Cancer Genetics in 2019 to translate cancer susceptibility gene discoveries to the clinic and the population.

The UPDB continues to grow, giving Huntsman Cancer Institute researchers access to one of the richest genealogic databases in the world linked to medical records. Today, the UPDB contains information on more than 11 million people.

And today, Huntsman Cancer Institute is the only cancer center in the country that houses a genetic counseling shared resource as a feature of its cancer center support grant infrastructure.

Utah researchers continue to engage families in studies that may power future genetic discoveries. Their generosity and willingness to participate in research make a big difference.

“From our experience, 99% of the people who we invite to participate in our studies will accept, and they will participate,” says Cannon-Albright. “As soon as you’re talking about genealogies and families, people are like, okay, [taking part in this study] might not help me. But if it can help my grandkids—then yes.”

These efforts are now powering population research that extends well beyond Utah. As a member of Oncology Research Information Exchange Network (ORIEN)—a network of the nation’s top cancer centers who have joined together to collaborate on cancer research projects—Huntsman Cancer Institute engages patients in studies that span beyond our campus across the globe. Patients are invited to donate samples of their tissues and participate in research studies seeking to improve cancer prevention and treatment outcomes. Incredibly, about 94% agree to participate, demonstrating an enormous commitment to cancer research.

The more the public, doctors, and researchers understand about cancer predisposition, the more those discoveries can be translated into personalized medical treatments and approaches to prevention, early detection, and survival, for patients now and in the future.