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

Cancer. 2016 Mar 1;122(5):766-72. doi: 10.1002/cncr.29812. Epub 2015 Dec 22.

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 has been 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.

Methods: Patients with metastatic lung adenocarcinomas from 14 US sites were enrolled in the LCMC1. Tumor samples were collected from 2009 through 2012 with multiplex genotyping performed on 10 oncogenic drivers (KRAS, epidermal growth factor receptor [EGFR], anaplastic lymphoma kinase (ALK) rearrangements, ERBB2 [formerly human epidermal growth factor receptor 2], BRAF, PIK3CA, MET amplification, NRAS, MEK1, and AKT1). Patients were classified as white, Asian, African American (AA), or Latino. The driver mutation frequency, the treatments, and the survival from diagnosis were determined.

Results: One thousand seven patients were included. Whites represented the majority (n = 838); there were 60 AAs, 48 Asians, and 28 Latinos. Asian patients had the highest rate of oncogenic drivers with 81% (n = 39), and they were followed by Latinos with 68% (n = 19), whites with 61% (n = 511), and AAs with 53% (n = 32). For AAs, the EGFR mutation frequency was 22%, the KRAS frequency was 17%, and the ALK frequency was 4%. Asian patients were most likely to receive targeted therapies (51% vs 27% for AAs). There were no significant differences in overall survival.

Conclusions: Differences were observed in the prevalence of oncogenic drivers in lung adenocarcinomas and in subsequent treatments among racial groups. The lowest frequency of drivers was seen for AA patients; however, more than half of AA patients had a driver, and those treated with targeted therapy had outcomes similar to those of other races. Cancer 2016;122:766-772. © 2015 American Cancer Society.

Keywords: disparities; genomics; lung cancer; race; targeted therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adenocarcinoma / ethnology
  • Adenocarcinoma / genetics*
  • Adenocarcinoma / pathology
  • Adenocarcinoma of Lung
  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Anaplastic Lymphoma Kinase
  • Asian / genetics
  • Black or African American / genetics
  • Brain Neoplasms / ethnology
  • Brain Neoplasms / genetics*
  • Brain Neoplasms / secondary
  • Class I Phosphatidylinositol 3-Kinases
  • ErbB Receptors / genetics
  • Ethnicity / genetics*
  • Female
  • GTP Phosphohydrolases / genetics
  • Hispanic or Latino / genetics
  • Humans
  • Liver Neoplasms / ethnology
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / secondary
  • Lung Neoplasms / ethnology
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MAP Kinase Kinase 1 / genetics
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / genetics
  • Proto-Oncogene Proteins B-raf / genetics
  • Proto-Oncogene Proteins c-akt / genetics
  • Proto-Oncogene Proteins c-met / genetics
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Receptor Protein-Tyrosine Kinases / genetics
  • Receptor, ErbB-2 / genetics
  • United States
  • White People / genetics
  • Young Adult

Substances

  • KRAS protein, human
  • Membrane Proteins
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • EGFR protein, human
  • ERBB2 protein, human
  • ErbB Receptors
  • MET protein, human
  • Proto-Oncogene Proteins c-met
  • Receptor Protein-Tyrosine Kinases
  • Receptor, ErbB-2
  • AKT1 protein, human
  • BRAF protein, human
  • Proto-Oncogene Proteins B-raf
  • Proto-Oncogene Proteins c-akt
  • MAP Kinase Kinase 1
  • MAP2K1 protein, human
  • GTP Phosphohydrolases
  • NRAS protein, human
  • Proto-Oncogene Proteins p21(ras)