Genomic newborn screening could identify some children at risk for early cancers

A major study conducted by researchers from Dana-Farber/Boston Children's Cancer and Blood Disorders Center and Mass General Brigham indicates that incorporating genetic testing into routine newborn screening could potentially identify infants at risk of early-onset cancers. Currently, newborns in the United States undergo screening for a few rare, treatable disorders using blood samples collected from the heel within 24 hours of birth.

However, genetic testing could allow for the detection of new or inherited mutations that predispose children to various cancers, similar to how it is used to identify at-risk adults for diseases like breast or colon cancer. Co-senior author Richard B. Parad, MD, MPH, explains that genomic newborn screening could serve as a platform to identify high-risk children and implement targeted surveillance protocols.

Lisa Diller, MD, who cares for families with inherited cancer risks, highlights the importance of early detection in children who carry familial mutations, as it can lead to earlier tumor discovery and treatment, potentially resulting in better outcomes and less toxic therapies. In the study, researchers analyzed the blood samples of 1,948 children born in Michigan who developed solid tumors or brain tumors by the age of 8.

They found pathogenic or likely pathogenic variants in 132 children, representing nearly 7% of the group. This work, published in Nature Communications, represents one of the largest population-based studies evaluating the feasibility of early cancer-risk gene detection through newborn DNA sequencing. The findings suggest that about 1 in 27,000 newborns might develop an early-onset cancer that could be predicted through genomic newborn screening, a prevalence comparable to some conditions already included in newborn screening programs.

The strongest associations were observed in cancers with clear inherited risk factors, such as medullary thyroid carcinoma linked to RET mutations and retinoblastoma associated with RB1 mutations. Across various cancers, 11% to 30% of cases carried detectable mutations in the genes studied. Children with these cancer-predisposing mutations were diagnosed with cancer significantly earlier than those without, with a median age of 14 months compared to 32 months.

For instance, retinoblastoma patients with RB1 mutations were diagnosed at 9 months on average, compared to 23 months for those without mutations. Early identification of these mutations could enable routine surveillance, such as regular eye exams for retinoblastoma patients, potentially improving vision outcomes and reducing the need for severe treatments like eye removal, chemotherapy, or radiation.

The researchers emphasize that these findings provide strong evidence for incorporating selected pediatric cancer-risk genes into expanded newborn screening programs, particularly when early detection can lead to more effective surveillance, earlier diagnosis, and less intensive treatment approaches.