A Genome-Wide Association Study Identifies Two Novel Susceptible Regions for Squamous Cell Carcinoma of the Head and Neck

Cancer Res. 2020 Jun 15;80(12):2451-2460. doi: 10.1158/0008-5472.CAN-19-2360. Epub 2020 Apr 10.


To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with P < 1 × 10-3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from databases of Genotypes and Phenotypes. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96 × 10-9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54 × 10-9 for the leading SNP rs142021700) was identified for hypopharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and expression quantitative trait loci analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of human leukocyte antigen loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. SIGNIFICANCE: Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Computational Biology
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • HLA-DQ beta-Chains / genetics*
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • Laryngeal Neoplasms / genetics*
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Quantitative Trait Loci
  • Squamous Cell Carcinoma of Head and Neck / genetics*
  • Young Adult


  • CCHCR1 protein, human
  • HLA-DQ beta-Chains
  • HLA-DQB1 antigen
  • Intracellular Signaling Peptides and Proteins