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Every person is a collection of genetic puzzle pieces. On their own, those pieces can be hard to understand, but together, those pieces come together to form the picture that is you.
Sometimes, one of those pieces doesn’t fit as it should. In genetics, even a small change can affect the bigger picture. That is how inherited cancer risk can work: a change in a person’s genetic code can increase the likelihood of a life-changing diagnosis.
But what if you could predict your risk? Or know whether your child — and their children — would be affected by the same errant gene? Are there steps you could take to catch it early or even reduce the risk of getting cancer in the first place?
Those are the questions that inspired Project Inherited Cancer Risk (PICR), an innovative clinical study out of the DanceBlue Pediatric Hematology & Oncology Clinic at Golisano Children’s at UK. Advanced genetic testing identifies young patients with gene changes that increase their risk of cancer. With that knowledge, providers can formulate a personalized care plan for each patient, as well as determine if other family members carry a similar risk.
Looking for genetic clues
In 2018, shortly after he was named interim chief of pediatric oncology, John A. D’Orazio, M.D., Ph.D., noted an influx of inherited cancer referrals from Markey Cancer Center, UK HealthCare’s NCI-designated Comprehensive Cancer Center with its own robust cancer genetic testing program.
“The children of patients at Markey had a gene finding — a variant, we call it — that put them at increased risk of cancer,” said D’Orazio, now chief of pediatric oncology and the principal investigator of PICR. “Families got tested through what’s called cascade testing, where you see who else in the family might be affected. And then, lo and behold, a child will have the same gene finding. And so that child then needs care.”
With dozens of cancer syndromes that each require specialized expertise, it can be too much for the child’s general pediatrician to track through routine checkups. D’Orazio, along with Amanda Harrington, M.D., developed the Pediatric, Adolescent and Young Adult Inherited Cancer Predisposition Service to provide personalized care for those affected by an inherited cancer syndrome..
“We can miss about half of these patients that have an inherited cancer risk just by relying on clinical clues,” said D’Orazio. “My idea was to start a clinical study and offer it to patients who have been impacted by pediatric and young adult cancers and look for whether or not they might have one of these cancer syndromes because that information can affect how we treat them. It also has very big implications to the rest of the family.”
“We have some good clinical clues; there are certain tumors that happen in children that we know are likely to be associated with an inherited trait, but that’s not always the case,” said Harrington, medical director of the Pediatric, Adolescent and Young Adult Inherited Cancer Predisposition Service. “And family history is only as good as what people can remember or are willing to share. The person who receives this information has control over their own medical history, and it helps them make more informed decisions going forward.”
A microscopic look at the family tree
Project Inherited Cancer Risk looks for the answers to two questions in every patient tested: whether this cancer has a genetic component, and if other family members carry the same risk in their genes. About one in 10 children, adolescents and young adults diagnosed with cancer will have a genetic finding that puts them at risk for the disease.
James Collard is the genetic counselor at the DanceBlue Clinic and helps families understand the genetic testing process and what to do with the information it reveals.
“One thing we do is take a family tree and draw out what’'s called a pedigree for the family,” he said. Building from a detailed family history, a simple blood or saliva test can reveal risks lurking deep in a family’s genetic code. One mutation in one gene can have a cascading effect across generations. The genetics teams at UK HealthCare can mail out saliva kits to extended family members following their own genetic counseling sessions to help fill out the genetic picture.
Project Inherited Cancer Risk tests for a panel of genes, which Collard indicated is the most applicable option for many pediatric cancer patients. However, the DanceBlue Clinic also offers customized genetic testing that may be appropriate in more unique situations.
“We can trace changes through a family by determining a change in one person and then testing for that same single letter change in a relative. And then contrasting that with the volume of testing the whole genome,” Collard said. “So really the range of that is so incredible to think about.”
One important aspect Collard and Harrington stress to families is that having the genetic finding doesn’t mean someone will get cancer. Instead, they help families develop a plan to incorporate lifestyle changes that may mitigate the risks, as well as guidance on when to implement early detection screenings such as colonoscopies and mammograms.
Genetic testing hits close to home for Beau Lane. After his daughter Lauri died of the disease in 2012, he and his other two daughters underwent genetic testing. Testing showed that Beau carried a BRCA gene mutation that can increase the risk of breast cancer. One daughter’s breast cancer was caught early and successfully treated; the other chose a prophylactic mastectomy to reduce her risk. Their experience inspired Beau, and his wife Gale, to be early supporters of PICR.
“It is hard to explain the importance of this testing,” said Lane. “It is a matter of life and death. My family carries the BRCA gene and of my generation, there is only one of four branches that escaped it — including their children and grandchildren. Our support has helped fund genetic testing for children with cancer and made testing available for their entire family. There are several in my family who are alive today because of the technology and information they received.”
Knowledge is power
D’Orazio, Harrington and Collard know that just having this information is not enough; families need to understand it — and turn that understanding into action.
“The big misconception is when patients think that if the results come back positive, that they either have cancer or they're definitely going to get cancer,” said Collard. “It's an increased risk, but it's not a guarantee that one will get cancer.”
“We’'ve had cases where a child is diagnosed with a tumor, and they are the first in their family to develop this inherited cancer gene,” said Harrington. “Neither parent has this genetic variant in them, but it’'s important for that child as they grow up to know about the possibility of passing that on to their children.”
In other scenarios, the team can discover unexpected — and unrelated — cancer risks. While looking for the suspected genetic variant, testing can reveal an inherited cancer risk that may not explain the child’s diagnosis but could carry important implications for other family members, such as a parent’s risk for breast cancer.
Following National Comprehensive Cancer Network guidelines for each of the documented gene variants, the PICR team works with families on when they should undergo screenings and how often. Counseling, educational toolkits and other methods of patient support are tailored to each family, so they feel informed and supported every step of the way.
“It really is personal medicine,” said D’Orazio. “Dr. Harrington and James do a great job of making a plan that works. No two people have the same situation. Even if the same gene is found to be changed or mutated, there are characteristics of that individual that necessitate a personalized plan.”
Cures through collaboration
Families like the Lanes want to help ensure that more families can learn about inherited cancer risk early. Support from donors and Kentucky’s Pediatric Cancer Research Trust Fund help offset the cost of genetic sequencing which isn’t covered by most families’ insurance plans. The project expanded to include collaboration with Norton Children’s Hospital in Louisville. In October 2025, Kentucky Children’s Hospital joined the Golisano Children’s Alliance and became Golisano Children’s at UK. The alliance includes 21 other children’s hospitals across the nation, bringing together experts to expand what’s possible in pediatric care and research. One of Harrington’s projects is the pediatric germline molecular tumor board, a multidisciplinary effort that brings together providers and researchers to present their inherited risk findings to a group of oncologists, researchers, sequencers, genetic counselors and ethicists for discussion and recommendations.
“When we joined Golisano Children’s Alliance, one of the first things I did was to reach out to my colleagues at those other children’'s hospitals, let them know what we’'re doing here at UK, and invite them to be a part of it,” said D’Orazio. “Representatives from other children’'s hospitals are interested in taking part in the tumor board, with the invitation to extend Project Inherited Cancer Risk to our sister institutions.”
It’s one thing to have input from fellow physicians, researchers and genetic counselors, but, according to D’Orazio, some of the most vital feedback comes from the patients and families themselves. The fear of a cancer diagnosis lurks in the back of everyone’s mind, but for those with a family history or a positive genetic finding, that anxiety is amplified. Based on interviews and surveys, the PICR team worked with pediatric psychologists Meghan L. Marsac, Ph.D. and Tanesha Johnson, Ph.D. to provide resources to address families’ emotional needs. The team is also exploring creative ideas to help support families with genetic testing and subsequent surveillance and screening. At its heart, D’Orazio said this work is about giving children and families the knowledge they need to face cancer risk sooner, with clearer answers and more support.
“It’s exciting to hear what the cancer predisposition community could use, then actually have the resources and gumption to do it,” D’Orazio said. “When I think about the future of our program, I think about our ability to respond to a need that has not been met in our community.”
That kind of support can help families move from uncertainty to action, giving them a clearer sense of what their risk means and what they can do next.
“It is really empowering for families to know they carry this risk,” said Harrington. “It doesn’'t mean they are going to get cancer, but they have the choice of whether they want to participate in screening how they want to take care of their health and to catch any cancers at an early, more treatable stage. Does it come with some anxiety? Absolutely. But if we can be proactive and catch something as early as possible, all the better. It’'s helpful to be able to make informed decisions about your health, your children’'s health and your future.”
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To support Project Inherited Cancer Risk, enter “Pediatric Hematology/Oncology Inherited Cancer Program & Research Fund.”