权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

The role of germline and somatic DNA mutations in oral and oropharyngeal cancers

种系和体细胞 DNA 突变在口腔癌和口咽癌中的作用

基本信息

批准号：
9238815
负责人：
Paul Joseph Brennan
金额：
$ 65.03万
依托单位：
INTERNATIONAL AGENCY FOR RES ON CANCER
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-01-10 至 2021-12-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9238815
关键词：
6p21 Affect Alcohol consumption American Anatomy Biological Cancer Etiology Candidate Disease Gene Cervical Cessation of life Characteristics Clinical DNA Sequence Alteration Data Demographic Factors Development Diagnostic Disease Disease Outcome Early Diagnosis Early treatment Etiology Europe European Genes Genetic Genotype HLA Antigens Haplotypes Head and Neck Cancer Head and Neck Squamous Cell Carcinoma Human Papillomavirus Human papillomavirus 16 Incidence Life Style Malignant Neoplasms Malignant neoplasm of pharynx Mediating Modeling Mutation National Institute of Dental and Craniofacial Research Nature Neck Cancer Oral cavity Oropharyngeal Oropharyngeal Carcinogenesis Outcome Patients Pattern Pharyngeal structure Population Predisposition Prevalence Prevention Progression-Free Survivals Publishing Reporting Research Risk Risk Factors Role Sample Size Sampling Serologic tests Site Smoking Smoking History Somatic Mutation Squamous cell carcinoma Susceptibility Gene The Cancer Genome Atlas Tobacco use Variant actionable mutation age effect cancer genome cancer risk cancer survival cancer type clinically relevant disorder risk exome sequencing genetic association genome wide association study genomic profiles improved individualized prevention insight malignant mouth neoplasm malignant oropharynx neoplasm molecular marker novel oral infection outcome forecast screening sex study population targeted sequencing therapeutic candidate therapeutic target treatment strategy tumor

项目摘要

PROJECT SUMMARY/ABSTRACT Most cancers of the head and neck are squamous cell carcinomas (HNSCC) and the majority affects the oral cavity or pharynx. Tobacco use and alcohol consumption are the major risk factors and together account for approximately two-thirds of the cases. Oral infection with human papillomavirus (HPV) is an important independent risk factor for the development of oropharyngeal cancer (OPC); only 6% of other HNSCC sites are associated with HPV. Incidence of HPV-related OPC is increasing, most notably in the U.S. and Europe. Interestingly, and likely due to differences in etiology and related differences in tumor characteristics, HPV- positive [HPV(+)] tumors have a more favorable outcome than HPV-negative [HPV(-)] tumors. A recent large genome-wide association (GWA) study from this group identified multiple novel susceptibility loci for HNSCC, and in particular a strong role for the human leukocyte antigen (HLA) region in OPC. Further, recently completed tumor genome profiling efforts have provided important information on the somatic alterations present in HNSCC. However, only limited numbers of HPV(+) tumors were included and these studies have offered little insights into the clinical relevance of the identified alterations due to the limited nature of clinical and outcome data available. To improve understanding of the genetic factors involved in oral cancer (OC) and OPC risk and outcome, we will utilize samples and data from 5 well-annotated study populations to: (Aim 1) complete HPV analysis of 2,028 OPC cases in order to evaluate the relationship between germline variants, and in particular variants in the HLA region, and risk of HPV(+) OPC; (Aim 2) perform whole exome and targeted sequencing on 2,000 representative tumors (1,000 OCs, 1,000 OPCs) to further elucidate the driver mutations and potential therapeutic targets in OC and OPC, and to clarify potential mechanisms associated with lifestyle and infectious exposures for developing both cancers; and (Aim 3) utilize available outcome data on these 2,000 patients to evaluate the role of somatic alterations in OC and OPC in outcome, build prediction models for OC and OPC survival, and clarify the role of smoking in HPV(+) OPC outcome.

项目总结/文摘