Abstract
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 thetumour-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 thesusceptibility 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 inandvariant 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.
Overview
- The study focuses on the association between pathogenic genetic variants in the germline of individuals and an increased risk of developing lung cancer. The study identifies two major lung cancer susceptibility syndromes, Li-Fraumeni syndrome and inherited lung disease, and discusses the role of variants in the breast and pancreatic cancer susceptibility gene in lung adenocarcinoma risk. The study aims to provide criteria for referring lung cancer patients to the cancer genetics clinic and recommends lung cancer screening for asymptomatic carriers with thoracic magnetic resonance imaging at its core. The hypothesis being tested is that pathogenic genetic variants in the germline of individuals are associated with an increased risk of developing lung cancer.
Comparative Analysis & Findings
- The study compares the outcomes observed under different experimental conditions or interventions, specifically the identification of pathogenic genetic variants in patients with cancer and their relatives, and the recommendation of lung cancer screening for asymptomatic carriers with thoracic magnetic resonance imaging at its core. The study identifies two major lung cancer susceptibility syndromes, Li-Fraumeni syndrome and inherited lung disease, and discusses the role of variants in the breast and pancreatic cancer susceptibility gene in lung adenocarcinoma risk. The study finds that lung cancer screening should be offered to asymptomatic carriers, with thoracic magnetic resonance imaging at its core.
Implications and Future Directions
- The study's findings have significant implications for the field of research and clinical practice, as they provide criteria for referring lung cancer patients to the cancer genetics clinic and recommend lung cancer screening for asymptomatic carriers with thoracic magnetic resonance imaging at its core. The study identifies two major lung cancer susceptibility syndromes, Li-Fraumeni syndrome and inherited lung disease, and discusses the role of variants in the breast and pancreatic cancer susceptibility gene in lung adenocarcinoma risk. The study suggests that future research should focus on identifying additional genetic variants associated with lung cancer risk and developing more sensitive and specific screening tools for lung cancer. The study also highlights the importance of early detection and intervention for individuals with inherited lung disease, as cancer risk is increased in carriers independently of the underlying fibrosis.