title: Chronic Obstructive Pulmonary Disease Is Not Associated with KRAS Mutations in Non-Small Cell Lung Cancer.
abstract: Mutations in epithelial growth factor receptor (EGFR), as well as in the EGFR downstream target KRAS are frequently observed in non-small cell lung cancer (NSCLC). Chronic obstructive pulmonary disease (COPD), an independent risk factor for developing NSCLC, is associated with an increased activation of EGFR. In this study we determined presence of EGFR and KRAS hotspot mutations in 325 consecutive NSCLC patients subjected to EGFR and KRAS mutation analysis in the diagnostic setting and for whom the pulmonary function has been determined at time of NSCLC diagnosis. Information about age at diagnosis, sex, smoking status, forced vital capacity (FVC) and forced expiratory volume in 1 sec (FEV1) was collected. Chronic obstructive pulmonary disease(COPD) was defined according to 2013 GOLD criteria. Chi-Square, student t-test and multivariate logistic regression were used to analyze the data. A total of 325 NSCLC patients were included, 193 with COPD and 132 without COPD. COPD was not associated with presence of KRAS hotspot mutations, while EGFR mutations were significantly higher in non-COPD NSCLC patients. Both female gender (HR 2.61; 95% CI: 1.56-4.39; p<0.001) and smoking (HR 4.10; 95% CI: 1.14-14.79; p = 0.03) were associated with KRAS mutational status. In contrast, only smoking (HR 0.11; 95% CI: 0.04-0.32; p<0.001) was inversely associated with EGFR mutational status. Smoking related G>T and G>C transversions were significantly more frequent in females (86.2%) than in males (61.5%) (p = 0.008). The exon 19del mutation was more frequent in non-smokers (90%) compared to current or past smokers (36.8%). In conclusion, KRAS mutations are more common in females and smokers, but are not associated with COPD-status in NSCLC patients. EGFR mutations are more common in non-smoking NSCLC patients.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Ali
authors.initials: A
authors.lastname: Saber
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Anthonie J
authors.initials: AJ
authors.lastname: van der Wekken
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Gerald S M A
authors.initials: GS
authors.lastname: Kerner
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Maarten
authors.initials: M
authors.lastname: van den Berge
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Timens
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Arja
authors.initials: A
authors.lastname: ter Elst
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Anke
authors.initials: A
authors.lastname: van den Berg
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: T Jeroen N
authors.initials: TJ
authors.lastname: Hiltermann
authors.affiliation: Department of Pulmonary Diseases, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands.
authors.forename: Harry J M
authors.initials: HJ
authors.lastname: Groen
mesh_terms: D000368:Aged; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D005541:Forced Expiratory Volume; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D014797:Vital Capacity
chemical_list: C117307:KRAS protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras)