Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas Journal Article


Authors: Pham, D. K.; Kris, M. G.; Riely, G. J.; Sarkaria, I. S.; McDonough, T.; Chuai, S. K.; Venkatraman, E. S.; Miller, V. A.; Ladanyi, M.; Pao, W.; Wilson, R. K.; Singh, B.; Rusch, V. W.
Article Title: Use of cigarette-smoking history to estimate the likelihood of mutations in epidermal growth factor receptor gene exons 19 and 21 in lung adenocarcinomas
Abstract: Purpose Lung adenocarcinomas with mutations in exons 19 and 21 of the epidermal growth factor receptor gene (EGFR) demonstrate sensitivity to gefitinib or erlotinib. Investigators have reported an association between EGFR mutations and the amount and duration of cigarette smoking, with the highest incidence of mutations seen in never smokers. Methods EGFR exon 19 and 21 mutation status was determined in 265 tumor samples using direct sequencing, polymerase chain reaction (PCR), or PCR-based restriction fragment length polymorphism analysis. A detailed smoking history was obtained. Patients were categorized as never osmokers (< 100 lifetime cigarettes), former smokers (quit >= 1 year ago), or current smokers (quit< 1 year ago). Results We detected EGFR mutations in 34 (51%) of 67 never smokers (95% Cl, 38% to 64%), 29 (19%) of 151 former smokers (95% Cl, 13% to 27%), and two (4%) of 47 current smokers (95% Cl, 1% to 16%). Significantly fewer EGFR mutations were found in people who smoked for more than 15 pack-years (P <.001) or stopped smoking less than 25 years ago (P <.02) compared with individuals who never smoked. The number of smoking pack-years and smoke-free years predicted the prevalence of EGFR mutations (areas under receiver operating characteristic curve = 0.78 and 0.77, respectively). Conclusion The likelihood of EGFR mutations in exons 19 and 21 decreases as the number of pack-years increases. Mutations were less common in people who smoked for more than 15 pack-years or who stopped smoking cigarettes less than 25 years ago. These data can assist clinicians in assessing the likelihood of exon 19 and 21 EGFR mutations in patients with lung adenocarcinoma when mutational analysis is not feasible.
Keywords: survival; erlotinib; predictors; features; activating mutations; responsiveness; cancer patients; egfr mutations; tyrosine kinase domain; gefitinib sensitivity
Journal Title: Journal of Clinical Oncology
Volume: 24
Issue: 11
ISSN: 0732-183X
Publisher: American Society of Clinical Oncology  
Date Published: 2006-04-05
Start Page: 1700
End Page: 1704
Language: English
ACCESSION: WOS:000236783900009
DOI: 10.1200/jco.2005.04.3224
PROVIDER: wos
PUBMED: 16505411
Notes: --- - Article; Proceedings Paper - 41st Annual Meeting of the American-Society-of-Clinical-Oncology - MAY 17-21, 2005 - Orlando, FL - "Source: Wos"
Altmetric Score
MSK Authors
  1. Venkatraman Ennapadam Seshan
    285 Seshan
  2. Shaokun Chuai
    29 Chuai
  3. Duykhanh Thi Pham
    13 Pham
  4. Valerie W Rusch
    652 Rusch
  5. Bhuvanesh Singh
    206 Singh
  6. William Pao
    141 Pao
  7. Vincent Miller
    262 Miller
  8. Marc Ladanyi
    864 Ladanyi
  9. Gregory J Riely
    344 Riely
  10. Mark Kris
    598 Kris