Precision DNA methylation test to reduce oral cancer disparities in African Americans patients residing in low-resource settings

精密 DNA 甲基化测试可减少居住在资源匮乏地区的非裔美国人患者口腔癌的差异

• 批准号: 10706376
• 负责人: Rafael Guerrero-Preston
• 金额: $ 29.25万
• 依托单位: LIFEGENE-BIOMARKS, INC.
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-20 至 2024-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10706376
• 关键词: Aberrant DNA Methylation; Adult; African American; African American population; Alcohol consumption; Alcohols; Anatomy; Biological Markers; Biopsy; Black race; Businesses; Cancer Burden; Cause of Death; Chronic; Classification; Clinical; Combined Modality Therapy; DNA; DNA Methylation; DNA Sequence Alteration; Data; Dental; Detection; Developed Countries; Development; Diagnosis; Diagnostic; Disparity; Distant; Early Diagnosis; Epigenetic Process; Etiology; Evaluation; Event; Exhibits; Frequencies; Gender; Gene Expression; Gene Silencing; Genes; Genetic; Genetic Predisposition to Disease; Genomics; Head and Neck Squamous Cell Carcinoma; Hospitals; Human Papillomavirus; Hypermethylation; Incidence; Infection; Inflammation; Latino; Lesion by Stage; Link; Location; Low Income Population; Malignant Neoplasms; Metastatic Neoplasm to Lymph Nodes; Methylation; Modification; Molecular; Monitor; Mutation; Newly Diagnosed; Oncogenes; Operative Surgical Procedures; Oral Diagnosis; Oral Stage; Outcome; PAX5 gene; Patients; Performance; Preventive; Primary Neoplasm; Process; Prognosis; Prognostic Marker; Promoter Regions; Publishing; Race; Recommendation; Recording of previous events; Recurrence; Research; Resource-limited setting; Risk; Saliva; Salivary; Small Business Innovation Research Grant; Specificity; Survival Analysis; Survival Rate; TP53 gene; Technology; Testing; The Cancer Genome Atlas; Tissues; Tobacco; Tumor Cell Invasion; Tumor Promotion; Tumor Suppressor Genes; United States; Virus Diseases; Visit; advanced disease; cancer health disparity; cancer subtypes; commercialization; cost; diagnostic accuracy; early detection biomarkers; epigenomics; genetic testing; health difference; high risk; improved; low and middle-income countries; low income country; malignant mouth neoplasm; methylation biomarker; methylation testing; methylome; molecular subtypes; mouth squamous cell carcinoma; patient stratification; personalized screening; premalignant; prevent; prognostic; prognostication; promoter; risk stratification; rural area; rural patients; rurality; saliva sample; salivary assay; screening; social health determinants; tobacco control; tobacco exposure; tumor

Project Summary A diagnosis of Head and neck squamous cell carcinoma (HNSCC) includes many cancer subtypes. We will focus on the oral cavity squamous cell carcinoma (OSCC) subtype on the proposed project. OSCC is the 11th most common malignancy in the world. Despite advances in treatments, the 5-year survival rates for OSCC have not improved for the past 25 years. OSCC is a very aggressive tumor, and the majority of patients displays a locoregionally advanced disease at diagnosis, for which multimodality therapy is required. Tumor invasion, lymph node metastasis and high rates of locoregional recurrence, besides development of second primary tumors, are the leading causes of death for OSCC patients. At least 50% of patients with locally advanced OSCC develop locoregional or distant relapses, which usually occur within the first 2 years of treatment completion. Treatment in high-quality hospitals is associated with improved survival for patients with OSCC. However, African American patients are less likely to be treated in high-quality hospitals compared with non-Latino white patients in US, as well as poor patients worldwide. Most HNSCC cases worldwide are detected at later stage of cancer because screening is not routinely conducted, leading to disparities at diagnosis based on rurality, race, and gender, which can be reduced by targeted screening. OSCC is one of the tumors in which the most glaring disparities exist worldwide. The dramatic disparity in incidence rates between high- and low-income countries is due primarily to differential access to effective screening and pre- cancer, or preventive, treatment. Similar disparities also exist within developed countries like the US where the burden of OSCC is highest in low-income populations. OSCC molecular screening should be included in dental visits for adults because early detection of OSCC is associated with better survival. The development of OSCC is a multistep process requiring the accumulation of multiple DNA alterations, influenced by a patient's genetic predisposition as well as by environmental influences, including tobacco, alcohol, chronic inflammation, and infection with Human Papilloma Virus. DNA alterations consist of two major types: alterations in tumor suppressor genes, which promote tumor development when inactivated; and alterations in oncogenes, which promote tumor development when activated. Tumor suppressor genes can be inactivated through genetic events or by epigenetic modifications such as DNA methylation. Gene silencing by aberrant DNA methylation is an important epigenetic event in cancer development and progression, which has great potential as a biomarker for early diagnosis, tumor molecular subtyping, prognosis, monitoring, and therapy. In this Fast Track SBIR project, we propose to demonstrate the feasibility for the commercialization of a precision DNA methylation test, the OralMethDx Test, to stratify patients at high risk of OSCC. Our business plan is to evaluate the performance of the OralMethDx Test for two separate indications: A saliva test for risk stratification in screening and early detection; and tissue biopsy test for diagnosis and prognostication.

项目总结