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.
BACKGROUND
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.
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
Norihiro
N
Yamaguchi
Paul A
PA
Vanderlaan
Erik
E
Folch
David H
DH
Boucher
Hannah M
HM
Canepa
Michael S
MS
Kent
Sidharta P
SP
Gangadharan
Adnan
A
Majid
Olivier N
ON
Kocher
Michael A
MA
Goldstein
Mark S
MS
Huberman
Daniel B
DB
Costa
D000328:Adult; D001741:Black or African American / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D000077548:Anaplastic Lymphoma Kinase; D001213:Asian / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006785:Hospitals, University; D006801:Humans; D008175:Lung Neoplasms / Q000208:ethnology / Q000209:etiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009857:Oncogenes; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D057566:Self Report; D012907:Smoking / Q000009:adverse effects*; D014481:United States; D044465:White People / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
ALK; Anaplastic lymphoma kinase; EGFR; Epidermal growth factor receptor; KRAS; Lung cancer; Never smokers; Non-small-cell lung cancer