Smoking Status and Self-Reported Race Affect the Frequency of Clinically Relevant Oncogenic Alterations in Non-Small-Cell Lung Cancers at a United States-based Academic Medical Practice

Lung Cancer. 2013 Oct;82(1):31-7. doi: 10.1016/j.lungcan.2013.07.013. Epub 2013 Aug 7.

Abstract

Introduction: The identification of somatic genomic aberrations in non-small-cell lung cancer (NSCLC) is part of evidence-based practice guidelines for care of patients with NSCLC. We sought to establish the frequency and correlates with these changes in routine patient-tumor sample pairs.

Methods: Clinicopathologic data and tumor genotype were retrospectively compiled and analyzed from an overall cohort of 381 patient-tumor samples.

Results: Of these patients, 75.9% self-reported White race, 13.1% Asian, 6.5% Black, 27.8% were never-smokers, 54.9% former-smokers and 17.3% current-smokers. The frequency of EGFR mutations was 23.9% (86/359), KRAS mutations 34.2% (71/207) and ALK FISH positivity 9.1% (23/252) in tumor samples, and almost all had mutually exclusive results for these oncogenes. In tumors from White, Black and Asian patients, the frequencies of EGFR mutations were 18.4%, 18.2% and 62%, respectively; of ALK FISH positivity 7.81%, 0% and 14.8%, respectively; and of KRAS mutations 41.6%, 20% and 0%. These patterns changed significant with increasing pack-year history of smoking. In White patients, the frequencies of EGFR mutations and ALK FISH positivity decreased with increasing pack-year cohorts; while the frequencies of KRAS mutations increased. Interestingly, in Asian patients the frequencies of EGFR mutations were similar in never smokers and in the cohorts with less than 45pack-year histories of smoking and only decreased in the 45pack-year plus cohort.

Conclusions: The frequencies of somatic EGFR, KRAS, and ALK gene abnormalities using routine lung cancer tissue samples from our United States-based academic medical practice reflect the diverse ethnicity (with a higher frequency of EGFR mutations in Asian patients) and smoking patterns (with an inverse correlation between EGFR mutation and ALK rearrangement) of our tested population. These results may help other medical practices appreciate the expected results from introduction of routine tumor genotyping techniques into their day-to-day care of NSCLC.

Keywords: ALK; Anaplastic lymphoma kinase; EGFR; Epidermal growth factor receptor; KRAS; Lung cancer; Never smokers; Non-small-cell lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • African Americans / genetics
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Asian Americans / genetics
  • Carcinoma, Non-Small-Cell Lung / ethnology
  • Carcinoma, Non-Small-Cell Lung / etiology
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • DNA Mutational Analysis
  • ErbB Receptors / genetics*
  • European Continental Ancestry Group / genetics
  • Female
  • Gene Frequency
  • Hospitals, University
  • Humans
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / etiology
  • Lung Neoplasms / genetics*
  • Male
  • Middle Aged
  • Oncogenes
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Receptor Protein-Tyrosine Kinases / genetics*
  • Retrospective Studies
  • Self Report
  • Smoking / adverse effects*
  • United States
  • ras Proteins / genetics*

Substances

  • KRAS protein, human
  • Proto-Oncogene Proteins
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ErbB Receptors
  • Receptor Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins