A step closer to a personalised approach for Lynch syndrome
Menée à l'aide de données de "the International Mismatch Repair Consortium" portant sur 5 585 familles atteintes du syndrome de Lynch dans 22 pays, cette étude analyse la variation de la pénétrance du cancer colorectal chez les porteurs de variants pathogènes selon le sexe et le continent de résidence
Over the past few years, traditional, one-size-fits-all treatment approaches for cancer have been steadily replaced by those that personalise interventions to an individual's unique genetic, molecular, physiological, and environmental profile, seeking to identify effective management and therapeutic strategies for every patient. This change in approach is due, in part, to emerging technologies, such as DNA sequencing and proteomics, that have shown the existence of interindividual variation in disease processes. Personalised medicine has a pivotal role in the clinical management of patients, and, in particular, patients with pathogenic variants in cancer predisposition genes, such as the variants in DNA mismatch repair genes (ie, MLH1, MSH2, MSH6, and PMS2) that are associated with Lynch syndrome. Around 10–15% of early-onset colorectal cancers can be attributed to Lynch syndrome, an inherited predisposition condition with a population prevalence of one in 280 people. 1 Lynch syndrome-associated colorectal neoplasms tend to develop at younger ages and progress more rapidly to cancer than do sporadic colorectal cancers, 2 requiring more intensive surveillance. However, patient adherence to surveillance is suboptimal 3 and interval cancers do occur. 4 Existing guidelines 5 for the screening and surveillance of individuals with Lynch syndrome are based on average age-specific cumulative risk for cancer. However, these guidelines do not consider the fact that substantial heterogeneity exists among patients with the same colorectal cancer predisposing syndrome, presenting challenges for diagnosis and management. Insufficient prospective data have led current guidelines to rely on retrospective data from patient cohorts whose selection for molecular testing was biased.