Germline risk of oral and oropharyngeal cancers across diverse populations

项目摘要/摘要 头颈部癌鳞状细胞癌(HNSCC)的发病率存在显著的地域差异 全球范围内。一些最高发病率出现在南欧、东欧和南欧。 美国。这些地区的HNC负担持续较高，需要强大的协作网络来 评估跨祖先背景和祖先背景内的易感基因座。此应用程序汇集了领先的 拥有大量具有良好特征的研究人群的国际组织，以调查生殖系的作用 在HNC TO最大的全基因组关联(GWA)研究中口腔和咽癌的变异 约会。来自6035个病例和6585个对照的先前数据将与最近生成的数据相结合， 由NIDCR和遗传病研究中心(CIDR)支持，来自IARC的4项多中心研究 来自加拿大、美国、英国、南美和伊朗的7项研究。总共11378例患者的基因分型数据 拟议工作中包括12,335项控制措施。此外，人类乳头瘤病毒(HPV)的状态将是 可用于所有4,454例口咽癌病例，允许按这一重要风险进行强大的分层分析 因素。最后，这里包括的不同人口将允许识别跨种族和人口- 用特定的生殖系易感性变异来表征对不同风险的HNC的易感性 人口。拟议的项目将确定与HNSCC风险有关的遗传因素在 欧洲、北美、南美和中东人口可能导致更早的 全球HNSCC的检测和改进的预防和治疗战略。

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.