Patrick R Benusiglio, Vincent Fallet, Mateo Sanchis-Borja, Florence Coulet, Jacques Cadranel
Author Information
Patrick R Benusiglio: UF d'Oncogénétique clinique, Département de Génétique et Institut Universitaire de Cancérologie, DMU BioGeM, GH Pitié-Salpêtrière, AP-HP, Sorbonne Université, Paris, France.
Vincent Fallet: Service de Pneumologie et Oncologie Thoracique, DMU APPROCHES, Hôpital Tenon, AP-HP, Sorbonne Université, Paris, France.
Mateo Sanchis-Borja: Service de Pneumologie et Oncologie Thoracique, DMU APPROCHES, Hôpital Tenon, AP-HP, Sorbonne Université, Paris, France. ORCID
Florence Coulet: Sorbonne Université, INSERM, Unité Mixte de Recherche Scientifique 938 et SIRIC CURAMUS, Centre de Recherche Saint-Antoine, Equipe Instabilité des Microsatellites et Cancer, Paris, France. ORCID
Jacques Cadranel: Service de Pneumologie et Oncologie Thoracique, DMU APPROCHES, Hôpital Tenon, AP-HP, Sorbonne Université, Paris, France jacques.cadranel@aphp.fr.
Pathogenic genetic variants (formerly called mutations) present in the germline of some individuals are associated with a clinically relevant increased risk of developing lung cancer. These germline pathogenic variants are hereditary and are transmitted in an autosomal dominant fashion. There are two major lung cancer susceptibility syndromes, and both seem to be specifically associated with the adenocarcinoma subtype. Li-Fraumeni syndrome is caused by variants in the tumour-suppressor gene. Carriers are mainly at risk of early-onset breast cancer, sarcoma, glioma, leukaemia, adrenal cortical carcinoma and lung cancer. variants, T790M in particular, cause the susceptibility syndrome. Risk seems limited to lung cancer. Emerging data suggest that variants in , the breast and pancreatic cancer susceptibility gene, also increase lung adenocarcinoma risk. As for inherited lung disease, cancer risk is increased in and variant carriers independently of the underlying fibrosis. In this review, we provide criteria warranting the referral of a lung cancer patient to the cancer genetics clinic. Pathogenic variants are first identified in patients with cancer, and then in a subset of their relatives. Lung cancer screening should be offered to asymptomatic carriers, with thoracic magnetic resonance imaging at its core.
