Germline risk of oral and oropharyngeal cancers across diverse populations

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PROJECT SUMMARY/ABSTRACT There is striking geographical variation in head and neck cancer squamous cell carcinoma (HNSCC) incidence globally. Some of the highest incidence rates have been observed in Southern and Eastern Europe and South America. The continual high HNC burden in these regions necessitates strong collaborative networks to assess susceptibility loci across and within ancestral backgrounds. This application brings together leading international groups with large, well characterized study populations, to investigate the role of germline variation in oral cavity and pharynx cancer in the largest genome-wide association (GWA) study of HNC to date. Previous data from 6035 cases and 6585 controls will be combined with recently generated data, supported by NIDCR and the Center for Inherited Disease Research (CIDR), from 4 IARC multi-center studies and 7 studies from Canada, US, UK, South America and Iran. Genotyping data from a total of 11,378 cases and 12,335 controls are included in the proposed work. Additionally, human papillomavirus (HPV) status will be available for all 4,454 oropharynx cancer cases, allowing a powerful stratified analysis by this important risk factor. Finally, the diverse populations included here will allow for identification of trans-ethnic and population- specific germline susceptibility variants to characterize susceptibility to varying risk for HNC across populations. The proposed project will define the role of the genetic factors involved in risk of HNSCC in European, North American, South American and Middle Eastern populations which may result in earlier detection and improved prevention and treatment strategies for HNSCC globally.