MedicalResearch.com Interview with: Dr. Azi  Gazdar, MD UT Southwestern Medical Center W. Ray Wallace Distinguished Chair in Molecular Oncology Research Hamon Center for Therapeutic Oncology, Pathology MedicalResearch.com: What are the main findings of the study? Dr. Gazdar: We describe the characteristics of lung cancers arising in subjects who inherited a germline mutation that predisposes to lung cancer.  The mutation is rare in the general populations, and is inherited equally by both sexes.  However it is a potent predisposing gene, and one third of the never smoking carriers will develop lung cancer.  Thus, about 1% of patients who develop lung cancer carry the germline mutation.  This figure may rise as awareness of the condition and its link to lung cancer is raised among doctors diagnosing lung cancer. However, lung cancers mainly develop in women who are lifetime never smokers.  Lung cancer development is much less common among smokers and men, although accurate figures are not yet available. So the risk among carriers is somewhat similar to the BRCA genes predisposing to breast cancer, where a female carrier has about a 50% lifetime chance of developing breast cancer. The specific germline mutation (known as T790M) occurs in a gene known as epidermal growth factor receptor (EGFR) gene.  Sporadic mutations in this gene usually predict for effective responses to a class of drugs known as tyrosine kinase inhibitors (TKIs), which are widely used in the treatment of lung cancer.  However, the T790M mutation, when it occurs in sporadic tumors not associated with germline inheritance are resistant to TKI therapy.  Thus the prediction is that lung cancers arising in carriers with the germline mutation would also be resistant to TKI therapy. (more…)