Role of race in oncogenic driver prevalence and outcomes in lung adenocarcinoma: Results from the Lung Cancer Mutation Consortium

Abstract

BACKGROUND The discovery of oncogenic drivers has ushered in a new era for lung cancer, but the role of these mutations in different racial/ethnic minorities is understudied. The Lung Cancer Mutation Consortium 1 (LCMC1) database was investigated to evaluate the frequency and impact of oncogenic drivers in lung adenocarcinomas in the racial/ethnic minority patient population. PATIENTS AND METHODS Patients with metastatic lung adenocarcinomas from 14 United States sites enrolled in the LCMC1. Tumor samples were collected from 2009 through 2012, with multiplex genotyping performed on 10 oncogenic drivers (KRAS, EGFR, ALK rearrangements, ERBB2 (formerly HER2), BRAF, PIK3CA, MET amplification, NRAS, MEK1, AKT1). Patients were classified as Caucasian, Asian, African-American (AA), and Latino. Driver mutation frequency, treatments, and survival from diagnosis were determined. RESULTS 1007 patients were included. Caucasians represented the majority with N=838, AA N=60, Asians N=48, and Latinos N=28. Asian patients had the highest rate of oncogenic drivers with 39 (81%), followed by Latinos 19 (68%), Caucasians 511 (61%) and AA 32 (53%). In AA, EGFR mutation frequency was 22%, KRAS 17%, and ALK 4%. Asian patients were most likely to receive targeted therapies (51%), compared to 27% in AA. There were no significant differences in overall survival. CONCLUSIONS Differences are observed in the prevalence of oncogenic drivers in lung adenocarcinomas and consequent treatments among racial groups. The lowest frequency of drivers was seen in AA patients; however, over half of AA patients had a driver and those treated with targeted therapy outcomes similar to those of other races.

miRNAs associated with the malignant transformation of non-small cell lung cancer

“…Despite of improvements in clinical strategies, the 5-year survival rate after curative treatment is still very poor [1,2]. KRAS mutations were found to be significantly more frequent in adenocarcinoma patients [3].…”

Racial Disparities in the Molecular Landscape of Cancer

“…Nevertheless, some of the observed differences may be representative of a difference in pathogenesis of cancer in AA as compared with CC patients. These differences could potentially help elucidate possible causes for increased mortality in AA patients, which currently remain unclear (18). Thus, additional research with larger cohorts should aid in further describing these differences.…”

“…possibly responsive to a targeted therapy (20–24). Thus, it is important to ensure that all cancer patients, regardless of race, undergo genomic profiling in order to be treated with appropriate targeted therapies (18). …”

Are there any differences in genomic characterization of non-small cell lung cancer between African Americans and Whites?

“…Steuer et al recently reported the results from the Lung Cancer Mutation Consortium (n=60 for African Americans and n=838 for Whites), which were similar to those of this study. They noted a lower frequency of oncogenic driver mutations in African Americans patients than in Whites after adjusting for smoking by a multivariate analysis, although the sample size of their study was also too small to obtain statistical significance (odds ratio 0.69; 95% confidence interval, 0.41-1.18; P=0.176) (18).…”

“…Subsequent studies showed that the frequency of EGFR mutations was high in Asians (50-60%) and low in Whites (10-20%), but their frequency in African Americans varied with reports (15)(16)(17). The nature and frequency of other oncogenic driver mutations in NSCLC among African Americans have been rarely reported (18,19).…”