TY - JOUR
T1 - A genome-wide association study identifies two novel susceptible regions for squamous cell carcinoma of the head and neck
AU - Shete, Sanjay
AU - Liu, Hongliang
AU - Wang, Jian
AU - Yu, Robert
AU - Sturgis, Erich M.
AU - Li, Guojun
AU - Dahlstrom, Kristina R.
AU - Liu, Zhensheng
AU - Amos, Christopher I.
AU - Wei, Qingyi
N1 - Funding Information:
The replication data were from the study of OncoArray: Oral and Pharynx Cancer (dbGaP study accession no.: phs001202.v1.p1) in dbGaP. Genotyping performed at the CIDR was supported through contract number HHSN268201200008I: funds were provided by the U.S. National Institute of Dental and Craniofacial Research grant X01HG007780; funds were also provided by the NCI for genotyping for shared controls with the Lung OncoArray initiative (grant X01HG007492). University of Pittsburgh head and neck cancer study: grants P50 CA097190 and P30 CA047904. Carolina Head and Neck Cancer Study: R01-CA90731. GENCAPO: FAPESP, grant numbers 04/12054-9 and 10/51168-0. HN5000 study: NIHR RP-PG-0707-10034. Toronto study: the Canadian Cancer Society Research Institute (020214) and NCI U19 CA148127. ARCAGE study: European Commission's 5th Framework Program (QLK1-2001-00182), FIRMS, Region Piemonte, and Padova University (CPDA057222). Rome Study: AIRC IG 2011 10491 and IG2013 14220, and Fonda-zione Veronesi. IARC Latin American study: European Commission INCO-DC IC18-CT97-0222, Fondo para la Investigacion Cientifica y Tecnologica (Argentina), and Fundac¸ão de Amparo à Pesquisa do Estado de São Paulo (01/01768-2). IARC Central Europe study: INCO-COPERNICUS Program (IC15-CT98-0332), and NCI CA92039 and WCRF99A28. IARC Oral Cancer Multicenter study: Europe against Cancer (S06 96 202489 05F02), Spain FIS 97/0024, FIS 97/0662, BAE 01/5013, UICC Yamagiwa-Yoshida, National Cancer Institute of Canada, AIRC, and PAHO/WHO. EPIC study: European Commission (DG SANCO) and IARC.
Funding Information:
Part of the control were requested from the SAGE in dbGaP. Funding support for the SAGE was provided through the NIH Genes, Environment and Health Initiative (GEI, U01 HG004422). SAGE is one of the GWASs funded as part of the Gene Environment Association Studies (GENEVA) under GEI. Assistance with phenotype harmonization and genotype cleaning, as well as with general study coordination, was provided by the GENEVA Coordinating Center (U01 HG004446). Assistance with data cleaning was provided by the National Center for Biotechnology Information. Support for collection of datasets and samples was provided by the Collaborative Study on the Genetics of Alcoholism (U10 AA008401), the Collaborative Genetic Study of Nicotine Dependence (P01 CA089392), and the Family Study of Cocaine Dependence (R01 DA013423). Funding support for genotyping, which was performed at the Johns Hopkins University Center for Inherited Disease Research, was provided by the NIH GEI (U01HG004438), the National Institute on Alcohol Abuse and Alcoholism, the National Institute on Drug Abuse, and the NIH contract “High throughput genotyping for studying the genetic contributions to human disease” (HHSN268200782096C). The datasets used for the analyses described in this article were obtained from dbGaP at http://www.ncbi.nlm.nih.gov/projects/gap/ cgi-bin/study.cgi?study_id=phs000092.v1.p1 through dbGaP accession number phs000092.v1.p.
Funding Information:
S. Shete was supported in part by the NIH grants 1R01CA131324 and R01DE022891; the Cancer Prevention Research Institute of Texas grants RP170259; the Barnhart Family Distinguished Professorship in Targeted Therapy; and Betty B. Marcus Chair in Cancer Prevention. S. Shete and J. Wang were supported in part by the Cancer Center Support grant P30CA016672. Q. Wei was supported by NIH grants 2R01 ES011740 and 1R01CA 131274 and the Duke Cancer Institute as part of the P30 Cancer Center Support grant (Grant ID: NIH/NCI CA014236).
Publisher Copyright:
© 2020 American Association for Cancer Research.
PY - 2020/6
Y1 - 2020/6
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85086524352&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85086524352&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-19-2360
DO - 10.1158/0008-5472.CAN-19-2360
M3 - Article
C2 - 32276964
AN - SCOPUS:85086524352
SN - 0008-5472
VL - 80
SP - 2451
EP - 2460
JO - Cancer Research
JF - Cancer Research
IS - 12
ER -