Germline risk of oral and oropharyngeal cancers across diverse populations

项目总结/摘要 头颈部鳞状细胞癌（HNSCC）的发病率存在显著的地理差异 在全球据观察，南欧和东欧以及南欧国家的发病率最高， 美国参考这些地区持续的高HNC负担需要强大的合作网络， 评估祖先背景中的易感基因座。该应用程序汇集了领先的 具有大型，良好表征的研究人群的国际组，以研究生殖系的作用 在最大的HNC全基因组关联（GWA）研究中， 约会来自6035例病例和6585例对照的先前数据将与最近生成的数据相结合， 由NIDCR和遗传疾病研究中心（CIDR）支持，来自4项IARC多中心研究 以及来自加拿大、美国、英国、南美和伊朗的7项研究。共有11，378例病例的基因分型数据 12，335个控件包含在拟议工作中。此外，人乳头瘤病毒（HPV）状态将被 所有4，454例口咽癌病例均可用，允许根据这一重要风险进行有力的分层分析 因子最后，这里包括的不同人口将允许识别跨种族和人口- 特异性生殖系易感性变异，以表征对不同HNC风险的易感性 人口。建议的项目将确定与HNSCC风险有关的遗传因素的作用， 欧洲、北美、南美和中东人群，可能导致更早 检测和改善全球HNSCC的预防和治疗策略。

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.