Cascade testing for hereditary cancer in Singapore: how population genomics help guide clinical policy

Hereditary Cancer makes up around 5–10% of all cancers. It is important to diagnose hereditary cancer in a timely fashion, as not only do patients require long-term care from a young age, but their relatives also require management. The main approach to capture at-risk relatives is cascade testing. It involves genetic testing of relatives of the first detected carrier of a pathogenic variant in a family i.e. the proband. The current standard of care for cascade testing is a patient-mediated approach. Probands are then advised to inform and encourage family members to undergo genetic testing. In Singapore, cascade testing is inefficient, around 10–15%, lower than the 30% global average. Here, we describe the cascade testing process and its effort to increase testing in Singapore. Precision Health Research, Singapore (PRECISE), was set up to coordinate Singapore’s National Precision Medicine strategy and has awarded five clinical implementation pilots, with one of them seeking to identify strategies for how cascade testing for hereditary cancer can be increased in a safe and cost-efficient manner. Achieving this will be done through addressing barriers such as cost, manpower shortages, exploring a digital channel for contacting at-risk relatives, and getting a deeper insight into why genetic testing gets declined. If successful, it will likely result in care pathways that are a cost-effective public health intervention for identifying individuals at risk. Surveillance and management of those unaffected at-risk individuals, if caught early, will result in improved patient outcomes, and further reduce the healthcare burden for the economy.