Discovery and Validation of Plasma DNA Methylation Biomarker for Detection of Stomach Cancer
Abstract
I aim to become a leading investigator in the field of stomach cancer genetic epidemiology, and my long-term research goal is to develop preventive strategies to reduce disease burden from this malignancy. My research strategy follows two main approaches: (i) to identify inherited genetic variants associated with cancer in population potentially suitable for screening, and (ii) to discover tumor biomarkers that can facilitate early diagnosis. My research has been focused on identification of heritable components related to cancer risk. The Horizon Award will allow me to (i) expand beyond my current focus to the area of cancer biomarkers and to better tailor my career path as a cancer epidemiologist; (ii) gain experience in the process of obtaining competitive research funding; (iii) enhance my ability to obtain a tenure-track position outside of NCI; and (iv) ultimately become an independent investigator with unique capabilities for "Genetic cancer research" on "Stomach Cancer," two of the Fiscal Year 2015 Peer Reviewed Cancer Research Program Horizon Award Topic areas. For my postdoctoral training in the Division of Cancer Epidemiology and Genetics (DCEG), National Cancer Institute (NCI), I am fortunate to have joined a prominent group of epidemiologists who apply innovative research tools in population-based studies focused on upper gastrointestinal (UGI) cancers. Stomach cancer is one of the most widely varying cancers across populations, and its genetic and environmental factors other than the causative bacteria Helicobacter pylori are poorly understood. Despite markedly declining incidence in recent decades, almost one million new cases of stomach cancer were estimated to have occurred in 2012, making it the fifth most common malignancy in the world after lung, breast, colorectal, and prostate cancer. Five-year survival for 2005-2011 in the United States was less than 30%, since stomach cancer is generally asymptomatic in early stages and has often metastasized by the time of diagnosis. In contrast, 5-year survival rates are almost 70% in South Korea and Japan where mass screening programs have been implemented and a large proportion of stomach cancer is detected in early stages. UGI endoscopy has been considered as the gold standard for diagnosis of stomach cancer, but endoscopy-based mass screening may not be feasible in relatively low-risk or less developed regions. Therefore, identification of biomarkers for early-stage disease is crucial to the development of effective screening strategies. Methylation of the cytosines in DNA is a chemical modification that does not change the underlying coding sequence. DNA methylation has been shown to be associated with gene inactivation and plays an important role in both physiological and pathological processes. Importantly, methylation status can be detected in DNA extracted from various body fluids. Accordingly, efforts to evaluate DNA methylation as disease biomarkers are underway in multiple cancers. In particular, a commercial test based on blood DNA methylation for detection of colorectal cancer is under review for approval by the US Food and Drug Administration. Our study aims to identify and validate plasma-based DNA methylation as a biomarker to detect stomach cancer. Previous studies in this area have tested opportunistically selected DNA methylation candidates and used suboptimal assay techniques for the low-abundance DNA extracted from body fluids. To overcome the shortcomings of previous efforts, we have developed a comprehensive and systematic method for candidate marker selection and used highly sensitive detection methods to measure DNA methylation at the single molecule level. Our ongoing study is testing the most promising top 10 candidates among plasma DNA samples extracted from stomach cancer cases and healthy controls in Poland. In the proposed study, we will validate these results among plasma DNA samples from stomach cancer cases and
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 31, 2017
- Source ID
- W81XWH1610529
Entities
People
- Hyuna Sung
Organizations
- National Cancer Institute
- United States Army