Reproductive decision-making in cancer susceptibility syndromes

Cancer susceptibility syndromes confer an increased lifetime risk of cancer and occur due to germline likely-pathogenic or pathogenic variants in a cancer susceptibility gene. Clinical Genetics services advise patients of ways to manage their future cancer risks, often prefaced with uncertainties due to poor understandings of individualised risk. For individuals/couples whose future offspring are at risk of a cancer susceptibility syndrome, different options are available depending on their preferences and circumstances, including prenatal diagnosis and preimplantation genetic testing. This review provides an overview of the most common cancer susceptibility syndromes, available reproductive options and a genetic counselling framework recommended to support individuals/couples in their decision-making. We describe complexities of decision-making involving moderate penetrance and sex-specific variable penetrance genes and explore associated ethical issues arising in this complex area of medicine.