Family history of lung cancer in never smokers with non-small cell lung cancer (NSCLC) and its association with tumors harboring epidermal growth factor receptor (EGFR) mutations.

Abstract

7579 Background: Inherited susceptibility to lung cancer is an understudied subject, however it has been described among never smokers (<100 cigarettes/lifetime). Never smokers with NSCLC comprise an important subgroup of patients enriched for tumors harboring oncogene aberrations in the EGFR and ALK genes. We aimed to better characterize the incidence of family history of lung cancer in the setting of routine tumor genotyping among never smokers with NSCLC. Methods: Clinicopathologic data plus tumor genotype (EGFR, KRAS, ALK) from 230 consecutive never smokers seen at Beth Israel Deaconess Medical Center and Dana-Farber Cancer Institute was compiled. We retrospectively analyzed the incidence of a family history of any cancer and lung cancer in these patients. Results: In our cohort, the average age was 56 years, 67% of the patients were women, 75% were white, 41% had advanced NSCLC and 87% had adenocarcinoma histology. In these tumors, 98/230 (43%) had an EGFR mutation, 16/155 (10%) had KRAS mutations and 27/127 (17%) had an ALK translocation. Family history of any cancer was common (57%) and specific family history of lung cancer was present in 42/230 cases (18%). Out of thecases with a family history of any cancer, 22/53 (41.5%) EGFR-mutated, 1/6 (17%) KRAS-mutated and 3/20 (15%) ALK-translocated cohorts had a family history of lung cancer. The rate of family history of lung cancer to family history of cancer was significantly higher in the EGFR-mutated cohort when compared to the ALK translocated plus KRAS-mutated cohorts (p=0.023). Conclusions: Family history of lung cancer is common in never smokers with NSCLC, and there seems to be a particular link in families in which the proband has an EGFR-mutated tumor. Further study of families with EGFR-mutated NSCLC may yield insights into the pathogenesis of this tumor type.