Assessing clinical utility of genomic risk stratification for cancer prevention: a systematic review

Background

Despite advances in genomics for cancer prevention, its clinical utility remains inadequately assessed. This study, conducted within the European Joint Action JANE2, synthesizes evidence on the clinical utility of genomic-based personalized preventive strategies.

Methods

We conducted a systematic review following Cochrane and PRISMA guidelines, including randomized controlled trials (RCTs) evaluating genomic-based risk stratification for primary and secondary cancer prevention. We searched PubMed, CENTRAL, and Scopus with no time restriction. Primary outcomes were behavioral changes, cancer incidence, and mortality. The protocol was registered on OSF: 10.17605/OSF.IO/53Z7G.

Results

We included 16 RCTs, primarily focusing on skin cancers (38%). In 31% of the studies, risk stratification was based on high-penetrance genetic variants, while 69% used polygenic risk scores (PRS) based on common low-penetrance variants. Overall, 45% of the outcomes assessed lifestyle or behavioral changes following polygenic risk communication, with improvements reported in only 32% of cases (e.g., sun exposure habits for melanoma risk). Cancer incidence was investigated in 40% of the outcomes, with a reduction observed in 38% of cases, primarily following the use of preventive medications, such as aspirin in patients with Lynch syndrome. Adherence to preventive strategies accounted for 15% of the outcomes, showing improvement in 53% of cases, particularly in prostate cancer screening participation and prophylactic surgery for ovarian cancer. No study evaluated proliferation biomarkers or mortality as outcomes.

Conclusions

Genomic testing shows promise to improve risk stratification and tailor cancer prevention, particularly for high-penetrance genes, already included in guidelines but not implemented in all EU Member states. Reductions in cancer incidence and improved preventive behaviors may support the clinical utility of these strategies.

Key messages

• Genomic risk stratification supports cancer prevention by enabling targeted screening and preventive interventions, particularly for high-risk individuals.

• Integrating genomic risk stratification into prevention programs requires strong evidence of clinical utility from high quality studies.