title: Family history of lung cancer in never smokers with non-small-cell lung cancer and its association with tumors harboring EGFR mutations.
abstract: BACKGROUND
  Inherited susceptibility to lung cancer is understudied. Never smokers are 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 among never smokers with NSCLC.
  
  
  METHODS
  Clinicopathologic data, tumor genotype, family history of cancer, and specifically family history of lung cancer from 230 consecutive never smokers was retrospectively compiled and analyzed.
  
  
  RESULTS
  In our cohort, the median age was 56 years, 67% were women, 75% were white, 59% had advanced NSCLC and 87% had adenocarcinoma histology. In these tumors, 98/230 (42%) had an EGFR mutation, 17/155 (11%) had KRAS mutations and 27/127 (21%) 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%). The percentage of cases with family history of lung cancer was higher in the EGFR mutated versus EGFR wild-type NSCLCs. Out of the cases with a family history of any cancer, 22/53 (41.5%) EGFR mutated, 1/5 (20%) KRAS mutated and 3/19 (15.5%) ALK translocated cohorts had a family history of lung cancer. The ratio 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=0.039).
  
  
  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 when compared to ALK translocated or KRAS mutated tumors. Further study of families with EGFR-mutated NSCLC may yield insights into the pathogenesis of this tumor type.
authors.affiliation: Department of Medicine, Division of Hematology/Oncology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors.forename: Elizabeth M
authors.initials: EM
authors.lastname: Gaughan
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Cryer
authors.forename: Beow Y
authors.initials: BY
authors.lastname: Yeap
authors.forename: David M
authors.initials: DM
authors.lastname: Jackman
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Costa
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008487:Medical History Taking; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012907:Smoking
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases