Germline risk of oral and oropharyngeal cancers across diverse populations

不同人群患口腔癌和口咽癌的种系风险

• 批准号: 10456323
• 负责人: SHAMA VIRANI
• 金额: $ 10.84万
• 依托单位: INTERNATIONAL AGENCY FOR RES ON CANCER
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-01 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10456323
• 关键词: Alcohol consumption; American; Anatomy; Antibodies; Architecture; Benchmarking; Biological Assay; Canada; Case-Control Studies; Cessation of life; Clinical; Data; Databases; Development; Early Diagnosis; Eastern Europe; Epidemiology; Ethnic Origin; Ethnic group; Etiology; Europe; European; Event; Funding Agency; Genetic; Genetic Predisposition to Disease; Genetic study; Genome; Genotype; HLA Antigens; HPV-High Risk; Haplotypes; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Head and neck structure; Hereditary Disease; Human Papilloma Virus-Related Malignant Neoplasm; Human Papillomavirus; Human papillomavirus 16; Immune response; Incidence; Infection; International; International Agency for Research on Cancer; Iran; Malignant Neoplasms; Malignant neoplasm of cervix uteri; Malignant neoplasm of pharynx; Maps; Measures; Methods; Middle East; Molecular Profiling; Multicenter Studies; National Institute of Dental and Craniofacial Research; North America; Oral cavity; Oropharyngeal Neoplasms; Pharyngeal structure; Population; Population Heterogeneity; Predisposition; Prevention; Prevention strategy; Proteins; Research; Research Personnel; Risk; Risk Factors; Role; Sampling; Serology; Site; South America; South American; Southern Europe; Specificity; Squamous cell carcinoma; Stage at Diagnosis; Subgroup; Susceptibility Gene; Time; Tobacco; Tobacco use; Tumor Tissue; United States; Variant; Work; alcohol exposure; base; cancer site; case control; genetic predictors; genome wide association study; geographic difference; improved; individualized prevention; malignant mouth neoplasm; malignant oropharynx neoplasm; multi-ethnic; novel; protective effect; risk variant; serological marker; study population; treatment strategy; tumor

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.

项目摘要/摘要 头部和颈部癌鳞状细胞癌（HNSCC）发病率有惊人的地理变化 全球。在南欧和东欧和南部已经观察到了一些最高的发病率 美国。这些地区的不断高HNC负担需要强大的协作网络才能 评估跨祖先背景和内部易感性基因座。该应用程序汇集了领导 国际团体具有较大的研究人群，以调查种系的作用 HNC与最大全基因组关联（GWA）研究中口腔和咽癌的变化 日期。来自6035个病例和6585个控件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个IARC多中心研究 以及加拿大，美国，英国，南美和伊朗的7项研究。总共来自11,378例病例的基因分型数据 拟议的工作中包括12,335个控件。此外，人类乳头瘤病毒（HPV）状态将是 适用于所有4,454例口咽癌病例，可通过这种重要风险进行强大的分层分析 因素。最后，此处包括的不同人群将允许识别跨种族和人口 - 特定的种系易感性变异以表征对​​HNC风险变化的敏感性 人群。拟议的项目将定义遗传因素在HNSCC风险中所涉及的作用 欧洲，北美，南美和中东人口可能会导致早期 全球HNSCC的检测和改进的预防和治疗策略。