Driver mutations determine survival in smokers and never-smokers with stage IIIB/IV lung adenocarcinomas Journal Article
| Authors: | Paik, P. K.; Johnson, M. L.; D'Angelo, S. P.; Sima, C. S.; Ang, D.; Dogan, S.; Miller, V. A.; Ladanyi, M.; Kris, M. G.; Riely, G. J. |
| Article Title: | Driver mutations determine survival in smokers and never-smokers with stage IIIB/IV lung adenocarcinomas |
| Abstract: | BACKGROUND: The authors previously demonstrated that never-smokers with stage IIIB/IV nonsmall cell lung cancer (NSCLC) lived 50% longer than former/current smokers. This observation persisted after adjusting for age, performance status, and sex. In this study, the authors hypothesized that smoking-dependent differences in the distribution of driver mutations may explain differences in prognosis between these subgroups. METHODS: In total, 293 never-smokers and 382 former/current smokers with lung adenocarcinoma who underwent testing for epidermal growth factor receptor (EGFR) mutations and v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations and rearrangements in anaplastic lymphoma kinase (ALK) between 2009 and 2010 were investigated. Clinical outcomes and patient characteristics were collected. Survival probabilities were estimated using the Kaplan-Meier method. Group comparison was performed with log-rank tests and Cox proportional hazards methods. RESULTS: Although the overall incidence of these mutations was nearly identical (55% never-smokers vs 57% current/former smokers; P =.48), there were significant differences in the distribution of mutations between these groups for EGFR mutations (37% never-smokers vs 14% former/current smokers; P <.0001), KRAS mutations (4% never-smokers vs 43% former/current smokers; P <.0001), and ALK rearrangements (12% never-smokers vs 2% former/current smokers; P <.0001). Among never-smokers and former/current smokers, the prognosis differed significantly by genotype. Patients who had KRAS mutations had the poorest survival. Smoking status, however, had no influence on survival within each genotype. CONCLUSIONS: Never-smokers and former/current smokers with lung adenocarcinomas were not homogeneous subgroups. Each was made up of individuals whose tumors had a unique distribution of driver mutations, which were associated with different prognoses, irrespective of smoking history. © 2012 American Cancer Society. |
| Keywords: | epidermal growth factor; adult; cancer survival; controlled study; aged; aged, 80 and over; middle aged; gene mutation; major clinical study; overall survival; mutation; proto-oncogene proteins; cancer staging; neoplasm staging; polymerase chain reaction; adenocarcinoma; lung neoplasms; epidermal growth factor receptor; gene locus; genetic variability; genotype; smoking; receptor, epidermal growth factor; oncogene; disease severity; lung adenocarcinoma; karnofsky performance status; gene rearrangement; receptor protein-tyrosine kinases; ras proteins; egfr gene; k ras protein; epidermal growth factor receptor kinase inhibitor; anaplastic lymphoma kinase; nonsmall cell lung cancer; kras gene; crizotinib; cancer prognosis; alk gene; never-smoker; v-ki-ras2 kirsten rat sarcoma viral oncogene homolog |
| Journal Title: | Cancer |
| Volume: | 118 |
| Issue: | 23 |
| ISSN: | 0008-543X |
| Publisher: | Wiley Blackwell |
| Date Published: | 2012-12-01 |
| Start Page: | 5840 |
| End Page: | 5847 |
| Language: | English |
| DOI: | 10.1002/cncr.27637 |
| PROVIDER: | scopus |
| PMCID: | PMC3424296 |
| PUBMED: | 22605530 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 3 December 2012" - "CODEN: CANCA" - "Source: Scopus" |
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