To identify pathogenic or likely pathogenic cancer-predisposition variants in newborns and estimate their association with early-onset cancers.
Approach:
Study Population: Investigators identified 1,948 pediatric patients born in Michigan from 1987 to 2020 who developed a malignant tumor by age 8 and had archived newborn dried blood spots.
Genomic Sequencing: Targeted next-generation sequencing was performed on 11 autosomal dominant cancer-predisposition genes.
Variant Detection: Pathogenic or likely pathogenic germline variants were detected in 7% of the patients (n = 132).
Key Findings:
RB1 variants accounted for 69 of the detected variants, followed by TP53 (24), SMARCB1 (8), and WT1 (7).
130 patients developed tumors associated with the affected gene.
1 in 27,000 newborns may develop early-onset solid or brain malignancy with a detected cancer-predisposition variant.
Patients with detected variants received a cancer diagnosis at a median age of 14 months compared to 32 months for non-carriers.
Limitations:
The study did not prospectively assess the impact of genomic newborn screening on clinical outcomes.
Lack of a large comparison cohort of cancer-free newborns tested with identical methods.
Findings may not be generalizable to populations with different ancestry or demographics.
The panel included only 11 genes, potentially underestimating the number of genetically at-risk newborns.
Conclusion:
The data support the potential for newborn screening for selected cancer-risk genes, but further prospective research is needed to evaluate clinical and public health effects.
