Genomic Newborn Screening Could Detect Childhood Cancer Risk

GENOMIC newborn screening could identify a subset of children at risk of developing early-onset cancer before symptoms emerge, according to a population-based analysis using archived newborn dried blood spots.

Researchers analysed DNA from newborn dried blood spots from a Michigan birth cohort spanning 1987–2020. The study identified 1,948 children who subsequently developed a solid or central nervous system malignancy by age eight and examined 11 genes associated with cancer predisposition.

Pathogenic or likely pathogenic germline variants were identified in 132 children, representing 6.8% of cases. The variants were found across genes including RB1, TP53, SMARCB1, WT1, RET, SUFU, PTCH1, DICER1, APC and PHOX2B.

The findings indicated that approximately one in 27,000 newborns developed an early-onset malignancy associated with a pathogenic or likely pathogenic variant.

Strong Gene-Tumour Associations Identified

The analysis found substantial variation in genetic predisposition across cancer types. Germline variants were identified in 100% of children with medullary thyroid carcinoma and 40% of those with retinoblastoma. Five additional diagnoses showed variant prevalence of 11–30%.

The researchers also found strong gene–tumour specificity, with the association between particular genetic variants and tumour types reaching statistical significance (P<0.001).

DNA extraction and targeted sequencing from a single dried blood spot were technically successful in 99.7% of samples, supporting the feasibility of incorporating genomic analysis into newborn screening workflows.

The authors noted that children with identified germline variants developed tumours at very young ages, suggesting that earlier recognition of predisposition could potentially enable surveillance and earlier detection.

Screening Potential Requires Further Evidence

Despite the findings, the study did not establish the cost-effectiveness or clinical outcomes of population-wide genomic screening for cancer predisposition. Potential challenges include psychological distress for families, surveillance burden, overdiagnosis and unnecessary interventions.

The analysis was also limited by the absence of an ideal cancer-free control cohort, incomplete demographic information and exclusion of some cancer predisposition genes, including those associated with leukaemia and autosomal recessive syndromes.

The researchers concluded that the results support further investigation of newborn screening for selected cancer-risk genes. Future studies using broader gene panels and larger, more diverse populations will be needed to determine which genetic variants should be included and how screening could be integrated into clinical practice.

Reference

Diller L et al. Population-based genomic detection of childhood cancer predisposition using newborn dried blood spots. Nat Commun. 2026;17:8183.

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