Lectura recomendada por la Dra. Adriana Dela Valle.
Conferencia 2017: “Cáncer Hereditario, de la genética molecular”
- Fuente: Hereditary Cancer in Clinical Practice (2023) 21:19. https://doi.org/10.1186/s13053-023-00263-3
- Autores: Møller et al.
Resumen: The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modifed our understanding of carcino‑genesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with diferent penetrance and expressivities: the four Lynch syndromes. No person has an“average sex “or a pathogenic variant in an“average Lynch syndrome gene” and results that are not stratifed by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic pro‑cesses: MSI producing abnormal cells, and the host’s adaptive immune system’s ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system’s capability to destroy MSI cancers. Colonoscopy surveil‑lance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer
