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.

A multidisciplinary team led by investigators at Vanderbilt University Medical Center has received a $4.2 million grant from the National Cancer Institute (NCI) to probe the genetics of colorectal adenomas — polyps that can develop into colon cancer — and to identify drug candidates that could reduce adenoma recurrence. 

Colorectal cancer is the second most common cause of cancer-related death in the United States, according to the NCI, part of the National Institutes of Health. Removing precancerous polyps during colonoscopy procedures significantly reduces the burden of colorectal cancer, but about 30% of patients who have a colorectal adenoma removed will develop recurrent adenomas. 

“Patients who have recurrent adenomas are at higher risk for developing cancer,” said Xingyi Guo, PhD, associate professor of Medicine in the Division of Epidemiology and lead principal investigator for the project. “We will integrate cutting-edge genomic research with real-world patient data from electronic health records, with the goal of translating genetic discoveries into actionable strategies to prevent colorectal cancer.” 

Zhijun Yin, PhD, MS, associate professor of Biomedical Informatics, is co-principal investigator for the four-year project. 

The team previously conducted genome-wide association studies (GWAS) of about 8,000 colorectal adenoma cases from European American and African American participants included in BioVU, VUMC’s de-identified DNA biobank and linked electronic health records. Using a large-scale analysis of electronic health records and pathology reports, the investigators also established the Vanderbilt Colonoscopy Cohort of colorectal adenoma cases after polyp removal, which includes 76,664 cases. 

With the new funding support, the team will extend its efforts to establish the largest-ever genetic study of colorectal adenoma, drawing on BioVU, the Mass General Brigham Biobank, and the NIH All of Us Research Program to include over 25,000 cases in European Americans and 6,500 cases in African Americans, with thousands of recurrences. African Americans are about 20% more likely to have colorectal cancer and about 40% more likely to die from it compared to other racial groups, according to the American Cancer Society. 

“Our approach will allow us to examine racial differences in adenoma recurrence and colorectal cancer risk,” Guo said. 

In addition to GWAS, the team will conduct transcriptome-wide, methylome-wide, and proteome-wide association studies to identify genes and proteins associated with colorectal adenomas and their recurrence. The investigators will integrate findings from these “omics” studies with electronic health record data from the Vanderbilt Colonoscopy Cohort and the Mass General Brigham Colonoscopy Cohort and use machine learning frameworks to identify candidate drugs that could prevent colorectal adenoma recurrence. They will test the most promising drug candidates in colorectal adenoma and cancer cells, patient-derived organoids, and animal models. 

“This project is an innovative integration of multiomics analyses with electronic health record-based real-world clinical evidence,” Yin said. “We anticipate that our findings will inform personalized colorectal polyp surveillance, guide therapeutic prevention strategies, and ultimately reduce the burden of colorectal cancer nationwide.” 

Guo holds a secondary appointment in the Department of Biomedical Informatics at VUMC, and Yin holds secondary appointments in the Department of Computer Science and the Department of Electrical and Computer Engineering at Vanderbilt University. Guo and Yin have both received NCI R37 MERIT Awards, which provide long-term grant support to outstanding investigators. 

Other collaborators for the new NCI grant (R01CA297582) include VUMC Department of Medicine investigators Wei Zheng, MD, PhD, MPH, Qiuyin Cai, MD, PhD, and Wanqing Wen, MD, MPH, Division of Epidemiology; Bhuminder Singh, PhD, Division of Gastroenterology, Hepatology and Nutrition; and Kristen Ciombor, MD, MSCI, Division of Hematology and Oncology; and Harvard T.H. Chan School of Public Health investigator Mingyang Song, ScD, Departments of Epidemiology and Nutrition.

The post New NCI-funded project targets polyp recurrence to prevent colon cancer appeared first on VUMC News.