Discovery at UUHS

Over a decade ago, scientists at the University of Utah capitalized on a long and rich history of genetic discovery. Some of the most renowned geneticists at the University created genetic technology and discovered more than 30 genes that cause major diseases, both common and rare. The ground breaking discoveries have impacted how breast cancer and colon cancer are diagnosed and treated, and the process of drug developmentand approvals worldwide. 

APC | Colon Cancer

Gregg Johnson’s mother died when she was 47, and his grandmother died at 42. Colon cancer killed them both. Gregg will die one day, but it won’t be from the same colon cancer that killed his mother and grandmother, because in 1987, University of Utah researchers identified mutations in the APC gene as the underlying cause of an inherited colon cancer predisposition known as familial adenomatous polyposis (FAP).

In this inherited syndrome, hundreds to thousands of pre-cancerous growths called adenomatous polyps form in the colon, usually beginning before a person is 16 years old. The lifetime risk of colon cancer for people with this inherited mutation is 100 percent. Scientists have since determined that an acquired or non-inherited mutation of the APC gene is also found in 85 percent of non-familial colon cancer. Colon cancer is the number two cancer killer in the United States.

Both Gregg and his brother have the APC mutation that causes FAP, and they are both screened frequently so doctors can catch any polyps early. Gregg has two sons and one grandson, so far, who may all chose to be tested in time Thanks to discoveries at the University of Utah Health Sciences, the Johnson family can choose to change their family history.

BRCA 1 and BRCA2 | Breast Cancer

In a May of 2013 New York Times op-ed piece, Angelina Jolie shared her experience undergoing a bilateral prophylactic mastectomy due to her high genetic risk for breast cancer. Mutations in two genes, BRCA1 and BRCA2, are the biggest cause of hereditary breast and ovarian cancer; through genetic testing, Jolie was found to have a mutation in the BRCA1 gene.

These mutations are rare in the general population, but Jolie’s family history was a significant clue that she was at high risk for having a BRCA1 or BRCA2 mutation. Her mother had both breast and ovarian cancer, and her maternal grandmother had ovarian cancer, all diagnosed at younger-than-average ages. While having a BRCA1 or BRCA2 mutation confers a high lifetime risk for developing certain cancers, individuals with these mutations have many options to address their cancer risks.

The University of Utah has a unique history related to the BRCA1 and BRCA2 genes. In the early 1990’s, researchers at the University helped to identify the genes after studying numerous Utah families with high incidences of breast and ovarian cancer. In 1994, researchers at UUHS successfully sequenced these genes and created test to determine patient’s risks for getting the disease. This discovery has saved thousands of lives and changed how patients and providers treat and prevent breast cancer worldwide.

HERG | FDA Drug Approvals

Every drug that receives FDA approval in the U.S.A., Europe, and China is tested against the HERG gene.

In 1985, an antihistamine called Seldane was brought to market in the United States and millions of prescriptions were filled for the drug. It was marketed as the first non-sedating antihistamine for treating common allergies. Five years later, reports of serious ventricular arrhythmias from patients taking Seldane in conjunction with several other medications motivated the FDA to warn physicians and patients alike of its risks, which include sudden death.

What happened between 1985 and 1995 was nothing short of remarkable. University of Utah Health Sciences researchers Mark Keating and Mike Sanguinetti realized the biological implications of the HERG gene. Specifically, mutations of the HERG gene cause inherited long QT syndrome—a condition that causes ventricular fibrillation (v-fib). Further, they realized that certain drugs, like Seldane, produce the same condition by blocking the potassium ion channel encoded by the HERG gene, thus causing v-fib.

Today, as result of research and genetic discovery done at the University of Utah, every drug developed by pharmaceutical companies seeking F.D.A. approval in the U.S., Europe and China is tested against the HERG gene. This knowledge saves lives of patients as well as millions of dollars for pharmaceutical companies. Current research as a result of these discoveries is now focusing on how to activate the HERG potassium channel that when mutated or blocked by drugs causes v-fib.

About the Author:

Joe BorgenichtDirector of Special Initiatives, Public Affairs at University of Utah Health Sciences

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