Association of variations in HLA class II and other loci with susceptibility to EGFR-mutated lung adenocarcinoma

Nat Commun. 2016 Aug 9:7:12451. doi: 10.1038/ncomms12451.

Abstract

Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10(-17), per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10(-9), per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics*
  • Adenocarcinoma of Lung
  • ErbB Receptors / genetics*
  • Forkhead Transcription Factors / genetics
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Histocompatibility Antigens Class II / genetics*
  • Humans
  • Lung Neoplasms / genetics*
  • Mutation / genetics*
  • Polymorphism, Single Nucleotide / genetics
  • Reproducibility of Results
  • Risk Factors

Substances

  • FOXP4 protein, human
  • Forkhead Transcription Factors
  • Histocompatibility Antigens Class II
  • ErbB Receptors