Vanderbilt University Medical Center offers access to new resources that help relatives connect and join forces to protect their families from inherited diseases. 

VUMC is one of the first cancer centers to partner with the ConnectMyVariant program, which offers resources for families with hereditary cancer risk. The resources make genetic medicine approachable, can help people discover distant relatives they didn’t know before, and can assist families in talking across dinner tables about a potentially sensitive topic. It’s akin to an ancestry game that allows people to amplify the family benefits of cancer prevention, and the person who starts it can be a superhero. 

To launch a connection search, someone with a specific gene variant signs up to meet others who share that variant. When people have the same gene variant, there is more than 90% chance they are related, even if it is several generations back. This begins the process of sharing stories with others who are likely to be relatives, discovering new connections with unknown relatives, and encouraging family members to get tested. The program is designed around the perspective and experience of lay people — not clinicians. It is an innovative approach to encourage genetic testing, and it’s needed, said Tuya Pal, MD, professor of Medicine in the Division of Genetic Medicine and Clinical Pharmacology at VUMC. 

“Family communication, which is the basis of what we call cascade testing, is hugely important,” said Pal, who is also Ingram Professor of Cancer Research and an associate director at Vanderbilt-Ingram Cancer Center. “BRCA genes were identified 30 years ago, but we’ve found maybe 20% of adults who are at risk for cancer. There’s a lot of adults walking around with a BRCA mutation. They could get ongoing prevention, but they don’t know it. This is a challenging nut to crack, but it is of huge public health relevance. If we can get to these people, we can save lots of lives.” 

BRCA1 and BRCA2 gene variants, which increase risk for breast, ovarian, pancreatic and prostate cancer, have received the most media attention. However, in recent years, several other gene mutations have been discovered that can also put people at risk for cancer. Pal stressed that people should seek genetic testing from reputable and accredited laboratories, which are different from many direct-to-consumer testing companies that offer testing for “recreational genetics.” While direct-to-consumer labs offer ancestry testing, sometimes they also delve into other genes; however, the quality of the data they provide is not always accurate for disease risk. For this reason, it is important to get tested through providers knowledgeable about genetic testing options, such as the Vanderbilt Hereditary Cancer Clinic. Insurance typically covers the cost for those at high risk, such as those with a personal history of specific cancers (and diagnosed at certain ages), family history of specific cancers, and those who already have a relative found to have a gene mutation. The tests, which can be done with either blood or saliva samples, cost about $250 for self-paying patients.  

Pal likens a gene mutation to a spelling mistake. 

“When we’re talking about an inherited predisposition, you can think of each gene as a big book, and a mutation is like a ‘spelling mistake’ in that book — leading to the gene not working quite right and thereby raising risk of certain cancers,” she said. “If you’ve got the same spelling mistake between two people, they are somehow related. People sometimes have trouble sharing broadly with family members, so this tool can make this experience of family communication and testing more enjoyable. You can connect with people you don’t know that are related from maybe eight generations ago.” 

ConnectMyVariant, which is operated as a nonprofit organization, was developed by Brian Shirts, MD, PhD, associate professor of Pathology, Microbiology and Immunology and of Biomedical Informatics, who was recruited to VUMC in December 2024. He is the service medical director of the Molecular Genetics Laboratories. 

“Scientific modeling has shown that if we could reach out to second and third cousins effectively of people with known variants, we could identify everyone who has a hereditary cancer risk,” said Shirts, who is also President of ConnectMyVariant’s Board of Directors. 

However, he stressed that ConnectMyVariant is not a research program or a direct clinical resource.  

“It’s an educational program,” Shirts said, noting that people should schedule a visit with a genetic counselor affiliated with a medical provider if they discover they have relatives with mutations that put them at increased risk for cancer.  

ConnectMyVariant offers educational resources for adult-onset hereditary diseases for which there are established preventive actions people can take. It is not intended for use by people younger than 18, so it does not offer resources for autosomal recessive pediatric diseases.  

“The way I like to think about what we offer is ‘If I talk to my relatives, are they going to be able to do something?’ If the answer is yes, and they can get genetic testing and do something that will improve their health, then that’s included,” Shirts said. 

The ConnectMyVariant program also offers participants access to resources for ancestry research, such as professional assistance from the Center for Family History and Genealogy at Brigham Young University.  

For individuals with inherited cancer predisposition, Vanderbilt-Ingram has the Inherited Cancer Registry (ICARE), which Pal founded in 2010. It has grown into one of the largest registries for inherited cancers, with almost 8,000 participants enrolled to date. Through the registry, the latest care and research updates are shared with participants by newsletter, email and links to presentations, and it is a way for people to be part of the larger research mission. 

Pal serves as vice chair of the National Comprehensive Cancer Network Genetics/Familial Guidelines Committee for Breast, Ovarian and Pancreatic Cancer. She leads a team of certified genetic counselors at the Vanderbilt Hereditary Cancer Clinic.

The post New resources help people take action to prevent inherited diseases appeared first on VUMC News.

One person in 10 over the age of 70 will experience an explosive, clonal growth of abnormal blood cells, called clonal hematopoiesis of indeterminant potential or CHIP, that increases the risk of blood cancer and death from cardiovascular, lung and liver disease. 

The risk of blood cancer differs significantly, however, depending upon whether patients with CHIP also develop cytopenia (low blood cell count). 

An analysis of genetic sequencing data from more than 34,000 people over a 17-year period by researchers at Vanderbilt University Medical Center has found that persistent cytopenia appears to be a critical step in the progression of CHIP to blood cancer. 

For patients with CHIP who developed cytopenia, the risk of progression to blood cancer was 10 times higher than it was for patients without cytopenia — a 1-in-200 chance per year versus 1 in 2,000, the researchers report in the June 2025 issue of the Lancet journal, eClinicalMedicine.  

These findings suggest that checking blood counts regularly may be an effective way to monitor patients with CHIP for their risk of developing blood cancer, and cytopenia-free survival may be a valuable endpoint for clinical trials aimed at preventing blood cancer in these patients.

“This work is the largest longitudinal analysis of its kind and provides a roadmap for identifying high-risk CHIP patients who may benefit from closer monitoring or early intervention,” said the paper’s corresponding author, Alexander Bick, MD, PhD, associate professor of Medicine and director of the Division of Genetic Medicine at VUMC. 

“It also lays the groundwork for more feasible and targeted clinical trials in blood cancer prevention,” he said. 

Bick is internationally known for his research on the genetics of blood disorders. He and his colleagues have advanced the understanding of somatic (non-inherited) mutations in blood stem cells that can trigger a potentially life-threatening clonal growth of abnormal cells known as CHIP.  

Blood cancer (myeloid neoplasm) results from the abnormal growth of myeloid (blood) cells in the bone marrow. The current study compared blood cancer rates in patients with CHIP who did not develop cytopenia, to those with both CHIP and concurrent, clonal cytopenia of undetermined significance. 

Led by the paper’s first authors, James Brogan, MD, MS, a resident physician in the Department of Medicine, and Ashwin Kishtagari, MD, assistant professor of Medicine in the Division of Hematology and Oncology, the study required large numbers. 

The researchers pulled genetic sequencing data from three major population-level cohorts: the National Institutes of Health (NIH) All of Us Research Program, the UK (United Kingdom) Biobank and VUMC’s biobank, BioVU. 

With roughly 350,000 DNA samples collected to date, BioVU is the world’s largest repository of genetic material linked to de-identified electronic health records (EHRs) based at a single academic center.  

Access to whole genome sequences linked to EHRs for more than 107,000 adults enrolled in BioVU between 2006 and 2023 was provided through the Alliance for Genomic Discovery (AGD), a unique endeavor to accelerate the application of large-scale genomics to biomedical science and therapeutic development. 

Launched in 2022 by Nashville Biosciences LLC, a wholly owned VUMC subsidiary, and the global DNA sequencing giant Illumina Inc., AGD now includes eight major pharmaceutical companies that support the development and availability of whole genome sequences for research aimed at identifying disease associations and targets for intervention. 

The report in eClinicalMedicine “is one of the first papers to leverage data from the BioVU/Alliance for Genomic Discovery whole genome sequencing effort,” Bick said. “It also highlights how at VUMC medical trainees are doing cutting-edge research while developing as physicians.” 

Between the three biobanks, the researchers had access to 805,000 whole genome sequences. From this pool, they identified 8,114 individuals with CHIP who did not develop cytopenia and 1,260 who did. These 9,374 cases were matched with 24,749 controls who did not have CHIP. 

The annual blood cancer progression rate for participants with CHIP who did not develop cytopenia was nearly the same as the rate observed in the control population without CHIP (0.06% versus 0.04%), whereas the rate was 10 times higher for those with both CHIP and cytopenia (0.5% per year). 

Approximately 13% of participants with CHIP developed a cytopenia within five years. Men, smokers and older individuals (over 64) were at a higher risk of developing cytopenia, as were those who had two or more mutations or any high-risk mutations associated with CHIP. 

“Given the substantial risk of cytopenia, patients with multiple high-risk features may benefit from regular monitoring for cytopenia progression,” the researchers concluded. The good news is that this five-year window before the development of cytopenia and blood cancer “provides an opportunity for early intervention with potential disease-modifying therapies,” they wrote.  

Treatments for cytopenia range from drugs that stimulate the production of certain blood cell types to bone marrow or stem cell transplants. 

Co-authors from the Bick lab included rheumatology fellow Robert Corty, MD, PhD, Yash Pershad, an MD-PhD student, and Brian Sharber, MS. Other VUMC co-authors included faculty members Brett Heimlich, MD, PhD, Leo Luo, MD, Brent Ferrell Jr., MD, Michael Savona, MD, and Yaomin Xu, PhD. 

This research was supported by NIH grants DP5OD029586, R01AG088657, R01AG083736, and P30CA068485, the Burroughs Wellcome Fund Career Award for Medical Scientists, the Edward P. Evans Foundation, and the Pew Charitable Trusts and the Alexander and Margaret Stewart Trust. 

Savona holds the Beverly and George Rawlings Directorship. Bick is supported in part by a Hevolution/AFAR New Investigator Award in Aging Biology and Geroscience Research, and Brogan is supported in part by an American Society of Hematology HONORS Award.

The post Low blood cell counts drive cancer in explosive blood disorder: study appeared first on VUMC News.