Study offers reassurance for patients with some cancer-linked genes

As more people receive genetic testing after a cancer diagnosis, newer variants have been identified that increase risk of developing cancer.

A study led by the University of Michigan Health Rogel Cancer Center finds that patients with three of these variants face no extra risk of dying from their cancer.

“Patients want to know: if they have one of these pathogenic variants, does that mean they’re more likely to die from their cancer?” said lead study author Christine Veenstra, M.D., MSHP, associate professor of hematology/oncology at Michigan Medicine.

“We found that these patients’ risk of dying of their cancer is the same as people who don’t have that pathogenic variant. It’s a good news message for those patients."

Germline genetic testing, which looks at inherited genes involved in cancer, can help determine treatment or follow up care for patients or identify family members who may be at higher risk of developing cancer.

Well known examples include BRCA1 and BRCA2, which are involved in breast, ovarian and pancreatic cancer, or Lynch syndrome, which is linked to colorectal cancer.

These genetic variants are often associated with different treatments and different outcomes for patients.

Mutations in the genes ATM, CHEK2 and PALB2 are known to increase risk of breast cancer, pancreatic cancer and colorectal cancer, but it wasn't known how those mutations affect a person’s risk of dying from those cancers.

This study, published in the Journal of Clinical Oncology, offers patients reassurance.

“We know a lot of people are getting germline genetic testing, and that a fair number of people will have one of these specific pathogenic variants. But we had no data to guide patients in terms of what that means for their personal risk of dying from cancer. We wanted to try to answer that question,” Veenstra said.

The researchers used data from the Surveillance, Epidemiology and End Results programs in Georgia and California, looking at a total of about 78,000 patients with breast, colorectal and pancreatic cancer diagnosed between 2013-2019 who also completed genetic testing at one of four specific laboratories.

Researchers have developed a partnership with these four genetic testing labs that allowed them to aggregate test results and specific pathogenic variants with patient outcomes.

After performing multiple statistical analyses, they found the risk of dying from breast, colorectal or pancreatic cancer was the same for patients with ATM, CHEK2 or PALB2 variants as for those without any genetic variant.

Veenstra noted that this analysis had not been done before because of the challenge of accessing this data.

The research team, led by Steven J. Katz, M.D., M.P.H., at the Rogel Cancer Center and Allison W. Kurian, M.D., M.Sc., at Stanford Medicine, has built a unique partnership to combine population-based SEER data with the data from the genetic testing companies.

“There isn’t another dataset like this that exists. It’s allowed interesting and clinically relevant studies like this to be done,” Veenstra said.

“This is a real issue patients face and a real fear that patients have when they see a pathogenic variant on their genetic testing result. This study will bring reassurance and relief to these patients.”

Additional authors: Paul Abrahamse, M.A.; Ann S. Hamilton, Ph.D.; Kevin C. Ward, Ph.D.; Scarlett L. Gomez, Ph.D.; Lihua Liu, Ph.D.; Steven J. Katz, M.D., M.P.H.; Timothy P. Hofer, M.D., M.Sc.; Allison W. Kurian, M.D., M.Sc.

Funding: National Cancer Institute grants CA283207, CA225697, CA163233, CA046592, CA251464

Paper cited: “Breast, Colorectal and Pancreatic Cancer Mortality with Pathogenic Variants in ATM, CHEK2 or PALB2,” Journal of Clinical Oncology. DOI: 10.1200/JCO-24-02442