Genomic screening uncovers hidden cancer and heart disease risk in young adults

A large Australian pilot shows that testing healthy young adults for high-risk genes can reveal serious disease risk years before symptoms appear, challenging traditional family history–based genetic testing.

Study: Feasibility and outcomes of the DNA Screen nationwide adult genomic screening pilot. Image Credit: Westlight / Shutterstock

In a recent study published in Nature Health, a group of researchers evaluated the feasibility, clinical uptake, and diagnostic yield of nationwide genomic screening in the adult population for medically actionable genetic conditions.

Rationale for Population Genomic Screening

What if a healthy 30-year-old could discover a life-threatening disease risk years before symptoms appear? Earlier, genetic testing in adults was dependent on a strong family history and severe personal illness, which left high-risk individuals undetected. But advances in genomic medicine have made this possible. Hereditary diseases like breast and ovarian cancer, hypercholesterolemia, and Lynch syndrome are very common, potentially life-threatening, and can often be prevented or mitigated if detected early, yet they frequently remain undiagnosed. Population genomic screening is one promising alternative, as it identifies genetic risk before disease onset and can guide preventive care. Healthcare systems are increasingly exploring large-scale genetic testing, but real-world evidence is essential to inform ethical, clinical, and economic decisions. Further research is needed to understand long-term outcomes, gene-specific disease penetrance in unselected populations, and downstream impacts of this approach.

Study Design and Recruitment Strategy

A prospective nationwide genomic screening pilot was conducted among Australian adults aged 18–40 years who had no prior genetic diagnosis of hereditary breast and ovarian cancer, Lynch syndrome, or familial hypercholesterolemia. Participants were recruited through national media coverage and then invited in stages to assemble a diverse cohort across geography, sex, cultural background, and socioeconomic status. Participants registered online, completed educational modules, passed a knowledge quiz, and provided informed consent before submitting saliva samples by mail.

Genetic Testing and Variant Reporting

DNA was extracted and analysed using a custom next-generation sequencing panel targeting ten high-risk genes associated with the three conditions. Only pathogenic or likely pathogenic variants were reported, following guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Variants of uncertain significance and benign variants were not disclosed to reduce unnecessary anxiety and clinical burden. The reported findings were research results that required confirmation in accredited clinical laboratories, and the assay did not detect large structural variants or copy number changes.

Clinical Follow-Up and Data Management

Participants with detected high-risk variants received telephone-based genetic counselling and were offered referral to specialist clinical genetics services or lipid clinics. Clinical teams collected family history, assessed eligibility for government-funded genetic testing, and arranged confirmatory testing through accredited diagnostic laboratories. Study data were managed using Research Electronic Data Capture software, and analyses were performed using the R statistical computing environment.

Participation Rates and Diagnostic Yield

Public engagement with the genomic screening initiative was substantial. More than 30,000 individuals registered within a short period following national media coverage, reflecting strong interest in proactive health information. Of these, 10,263 participants completed genomic screening, with a median age of 31.9 years. Just under half (45.5%) were male, and 30% were from culturally or linguistically diverse backgrounds, demonstrating a broad demographic reach.

Genetic screening identified pathogenic or likely pathogenic variants in 202 participants, representing about 2% of those tested. Variants in BRCA2 and LDLR were the most frequently detected, linked respectively to hereditary breast and ovarian cancer and familial hypercholesterolemia. No participant carried more than one high-risk variant. Almost all individuals (98.1%) had no prior personal diagnosis of a related clinical condition, highlighting the ability of genomic screening to identify hidden risk before disease is clinically recognised. However, the likelihood that a detected variant will cause disease may be lower in population-screened individuals than in families referred for clinical evaluation.

Clinical Uptake and Preventive Care Pathways

Clinical follow-up rates were high. Among participants who required referral, nearly all accepted the referral, and the majority attended specialist appointments. Genetic counselling supported understanding of results and facilitated entry into appropriate care pathways, where participants were typically advised on evidence-based risk management strategies, such as enhanced cancer surveillance or lipid-lowering interventions.

Limitations of Criteria-Based Genetic Testing

Another key finding was that 74.5% of participants who attended specialist clinics would not have qualified for government-funded genetic testing under existing criteria. Most had no personal disease history and often lacked a family history that would trigger testing. For cancer-associated variants, 72.6% were ineligible for testing based on current guidelines. Similarly, most participants with familial hypercholesterolemia variants had not previously met criteria for funded testing; 38.5% had not had cholesterol measured in the past year, and 63.5% were not receiving lipid-lowering therapy, despite many having elevated low-density lipoprotein cholesterol levels when assessed.

Family history proved to be an unreliable predictor of genetic risk. More than half of the participants with high-risk variants reported no affected first-degree relatives. This finding highlights a major limitation of criteria-based testing approaches and illustrates how reliance on family history alone can delay diagnosis and prevention.

Implications for Preventive Healthcare

From a real-world perspective, these findings have important implications. Early identification enables individuals to take preventive action well before clinical disease emerges, potentially reducing cancer incidence or cardiovascular events during early adulthood and midlife. At a population level, this approach may shift healthcare from reactive treatment to prevention, although longer-term follow-up is needed to assess impacts on health outcomes, healthcare utilisation, variant-specific penetrance, and costs.

Conclusions and Future Considerations

This nationwide pilot demonstrates that adult population genomic screening is feasible, highly acceptable, and clinically actionable within a public healthcare system. The programme successfully identified young adults at high genetic risk who would otherwise have remained undiagnosed under current testing frameworks. High clinical uptake and engagement indicate that individuals value early risk knowledge when appropriate counselling and follow-up care are provided. By revealing the limitations of family history-based testing, the findings illustrate how population genomic screening could reshape preventive healthcare, while underscoring the need for continued evaluation of long-term benefits, risks, penetrance uncertainty, and equity considerations.