The challenges of cascade genetic testing in hereditary cancer syndromes: A few ethical considerations.

Abstract

Progress in the discovery and understanding of cancer susceptibility genes and ever-cheaper genomic technologies are generating precious opportunities to optimize the identification of individuals with a hereditary cancer predisposition.Any such effort will have a more significant impact if it prioritizes those most at risk of developing cancer. This premise is central to cascade genetic testing, in which healthcare professionals encourage cancer patients carrying a predisposing gene variant to discuss the implications of their test results with their at-risk relatives so that, ideally, all the at-risk individuals in that family have the option to seek genetic counseling and testing in turn. Among the relatives found to have the gene variant, those who have developed cancer can then access targeted treatment and follow-up, those who are asymptomatic can benefit from enhanced preventive measures, while those who test negative can avoid unnecessary, costly, and time-consuming screening.Despite its life-saving potential, cascade genetic testing in hereditary cancer syndromes is often reported to have disappointing uptake rates, particularly among historically disadvantaged and underrepresented communities, for reasons that include barriers in intrafamilial genetic risk communication and low health and genetic literacy.This paper will discuss the challenges of cascade genetic testing in hereditary cancer syndromes, addressing some of the ethical questions arising from its current model, from strategies aimed at improving its uptake, as well as from alternative approaches to identifying asymptomatic individuals who may carry a cancer- associated pathogenic variant.