Genomic screening reveals hidden risk of cancer and heart disease in young adults

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

Study: Feasibility and results of DNA Screen’s national adult genome pilot. Image credit: Westlight / Shutterstock

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

Rationale for genomic population screening

What if a healthy 30-year-old could discover a life-threatening disease years before symptoms appear? Previously, genetic testing in adults depended on a strong family history and serious personal illness, which left high-risk individuals undetected. But advances in genomic medicine have made it possible. Hereditary diseases such as breast and ovarian cancer, hypercholesterolemia and Lynch syndrome are very common, potentially life-threatening and often preventable or curable if caught early, yet often go undiagnosed. Population genomic screening is a promising alternative, as it identifies genetic risk before disease onset and can guide preventive care. Health care 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 the long-term outcomes, the penetrance of the genetic disease in unselected populations, and the downstream effects of this approach.

Study Design and Recruitment Strategy

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

Genetic testing and reporting of variants

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

Clinical monitoring and data management

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

Participation Rates and Diagnostic Performance

Public participation in the genomic screening initiative was important. More than 30,000 people signed up within a short time after national media coverage, reflecting strong interest in preventive health information. Of these, 10,263 participants completed genomic testing, with a median age of 31.9 years. Just under half (45.5%) were male and 30% came from different cultural or linguistic backgrounds, demonstrating a broad demographic reach.

Genetic testing identified pathogenic or potentially pathogenic variants in 202 participants, representing approximately 2% of those screened. Variations on BRCA2 and LDLR were the most frequently detected, associated respectively with hereditary breast and ovarian cancer and familial hypercholesterolemia. No participant carried more than one high-risk variant. Almost all subjects (98.1%) had no previous personal diagnosis of a relevant clinical condition, highlighting the ability of genomic screening to identify hidden risk before the disease is clinically recognized. However, the probability that a detected variant will cause disease may be lower in population-screened individuals than in families referred for clinical evaluation.

Clinical Recruitment and Preventive Care Pathways

Clinical follow-up rates were high. Among participants who required a referral, almost all accepted the referral and the majority attended specialist appointments. Genetic counseling supported understanding of results and facilitated entry into appropriate care pathways, where participants were typically counseled 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-sponsored genetic testing according to existing criteria. Most had no personal history of illness and often no family history that would trigger screening. For cancer-related variants, 72.6% were not eligible for screening based on current guidelines. Similarly, most participants with familial hypercholesterolemia variants did not previously meet 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 an important limitation of criteria-based screening approaches and shows how reliance on family history alone can delay diagnosis and prevention.

Implications for preventive health care

From a real-world perspective, these findings have important implications. Early recognition allows individuals to take preventive measures long before clinical disease occurs, potentially reducing the incidence of cancer or cardiovascular events in early adulthood and middle age. At the population level, this approach may shift health care from reactive treatment to prevention, although longer-term follow-up is needed to assess effects on health outcomes, health care utilization, variant-specific penetrance, and costs.

Conclusions and future considerations

This nationwide pilot demonstrates that genomic screening of the adult population is feasible, highly acceptable, and clinically applicable in a public health care system. The program has successfully identified young adults at high genetic risk who would otherwise go undiagnosed under current testing frameworks. High clinical uptake and engagement suggest that individuals value early risk knowledge when appropriate counseling and follow-up care is provided. By revealing the limitations of family history-based testing, the findings show how population-based genomic testing could reshape preventive health care, while highlighting the need for continued assessment of long-term benefits, risks, uncertainty of penetrance, and equity.