Genome-Wide Study Of Head And Neck Cancer
Corina LESSEUR, International Agency for Research on Cancer, France
MCKAY J. 2
, ANANTHARAMAN D. 1
, JOHANSSON M. 1
, GABORIEAU V. 1
, CHABRIER A. 2
, WUNSCH-FILHO V. 3
, BOCCIA S. 4
, LACKO M. 5
, DIERGAARDE B. 6
, RAYJEAN H. 7
, NESS A. 8
, BRENNAN P. 1
1 Genetic Epidemiology Group (GEP), International Agency for Research on Cancer, Lyon, France
2 Genetic Cancer Susceptibility Group (GCS), International Agency for Research on Cancer, Lyon,France
3 University of Sao Paulo, Sao Paulo, Brazil
4 Section of Hygiene, Institute of Public Health, UniversitÓ Cattolica del Sacro Cuore, Rome, Italy
5 Department of Otorhinolaryngology, Head and Neck Surgery, Maastricht University Medical Center, Maastricht, The Netherlands
6 Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
7 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Canada.
8 School of Oral and Dental Sciences, University of Bristol, Bristol, UK
9 Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, NC, USA
Purpose: We sought to investigate novel genetic head and neck cancer (HNC) susceptibility loci in a large scale genome-wide association study (GWAS).
Methods: 6,034 cases and 6585 controls from 12 epidemiological studies including individuals from Europe, North and South America. Genotyping was carried out using the Illumina OncoArray a cancer-specific platform followed by genome-wide imputation of >7 million genetic variants. Overall HNC and site-specific, oral cancer (OC) and oropharyngeal cancer (OPC) associations were explored with multivariate unconditional logistic regression models adjusted for covariates and eigenvectors within geographical regions followed by fixed-effects meta-analysis.
Results: We detected 8 novel genetic loci (P<5 x 10-8) associated with HNC and/or OC and OPC. HNC was associated with 5p14.3 (rs79767424, RP11-124N3), a deletion at 10q26.13 (rs201982221, LHPP) and 11p15.4 (rs1453414, OR52N2/TRIM5). We also detected a large signal at 6p21.3 in the HLA class II associated with HNC and more strongly with OPC. For oral cancer, we identified genome-wide associations at 2p23.3 (rs6547741, GPN1) and 9q34.12 (rs928674, LAMC3). Additionally, two known neoplastic disease susceptibility regions 9p21.3 (CDKN2B-AS1) and 5p15.33 (CLPTM1L) were associated with oral cancer. Lastly, we confirmed previously described alcohol-related HNC susceptibility locus, ADH1B (4q23) that reached the significance threshold in the overall and site-specific analyses.
Conclusions: This large GWAS provides further genetic susceptibility associations for head and neck, oral and oropharyngeal cancer and highlights a strong effect of the HLA region in susceptibility to these cancers. Additional work is required to uncover biological mechanisms behind these findings.
Funding source: NIDCR 1X01HG007780-01, GWA study of oral and pharyngeal cancer based on the Oncochip. NCI 2R01CA092039-04A1, Genetics of tobacco and alcohol related cancers. Genetic Associations and Mechanisms in Oncology (GAME-ON) Initiative. IARC Fellowship Programme, partially supported by the European Commission FP7 Marie-Curie Actions (COFUND).