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

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 of 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 then 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.

Clinicopathological and Demographical Characteristics of Non-Small Cell Lung Cancer Patients with ALK Rearrangements: A Systematic Review and Meta-Analysis

“…Previous studies found similar overall distributions of ALK rearrangements between NSCLC patients of Asian and Caucasian descent [43], [76]. However in this meta-analysis, the prevalence of ALK rearrangements was heterogeneous between East Asians and Caucasians in terms of age, gender and histology.…”

Immunohistochemical Loss of LKB1 Is a Biomarker for More Aggressive Biology in KRAS-Mutant Lung Adenocarcinoma

“…Lung cancer patients with identified driver genomic alterations treated with a targeted therapy survive longer than those who did not receive a targeted therapy (2). KRAS mutations are the most prevalent oncogenic driver mutation, detected in 30% of smokers and 10% of never-smokers with lung adenocarcinoma in Western populations (3)(4)(5). In contrast, for patients with KRAS mutations, targeted therapies have been largely unsuccessful and chemotherapy remains the current standard of care.…”

Telomere Length of Human Adult Bronchial Epithelium and Bronchogenic Squamous Cell Carcinoma Measured Using Tissue Quantitative Fluorescence in situ Hybridization

“…The p53 mutation is significantly more frequent in lung carcinomas of smokers than in those of nonsmokers [18], and some papers have described widely dispersed p53 point mutations in the precancerous dysplastic bronchial epithelium of smokers [19,20]. On the other hand, EGFR mutations and ALK rearrangements are less common in smoking-related than in non-smoking-related lung cancer [21,22]. These reports and the results of the present study suggest that the mechanism of lung carcinogenesis in smokers differs from that in nonsmokers.…”