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

Authors

Sanjay Shete
Hongliang Liu
Jian Wang
Robert Yu
Erich M Sturgis
Guojun Li
Kristina R Dahlstrom
Zhensheng Liu
Christopher I Amos
Qingyi Wei

Publication Date

6-15-2020

Journal

Cancer Research

DOI

10.1158/0008-5472.CAN-19-2360

PMID

32276964

PMCID

PMC7299763

PubMedCentral® Posted Date

12-15-2020

PubMedCentral® Full Text Version

Author MSS

Published Open-Access

yes

Keywords

Adolescent, Adult, Aged, Aged, 80 and over, Computational Biology, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, HLA-DQ beta-Chains, Humans, Intracellular Signaling Peptides and Proteins, Laryngeal Neoplasms, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Squamous Cell Carcinoma of Head and Neck, Young Adult, Head and neck cancer, Case-control, Genome-wide association study, Genetic susceptibility, Single-nucleotide polymorphism

Abstract

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 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 dbGaP. 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 hypo-pharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and eQTL 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 HLA loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN.

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