The focus of my research is the molecular epidemiology of upper aerodigestive tract cancers;with a primary interest in the epigenetics of cancer, in particular DNA methylation, and its diagnostic and prognostic biomarker applications. My current research has concentrated on use of an array-based approach for the identification of DNA methylation markers for head and neck cancer. My career goal is to develop an externally funded research program and establish myself as an independent academic investigator in the field of molecular cancer epidemiology. To facilitate this progression, I am proposing the following translational research and career development plan through the NCI K22 Career Transition mechanism. Oral &pharyngeal cancer accounted for an estimated 39,400 new cancer diagnoses in 2011, with 7,900 people dying of the disease. The prognosis is relatively poor, with an overall 5-year survival around 60% that worsens with increasing stage at diagnosis. Oral &pharyngeal cancers have among the highest risk of 2nd primary cancer of all solid tumors, along with a very high rate of disease recurrence, which are a major reason for treatment failure. Additionally, oral &pharyngeal cancer patients frequently suffer from high morbidity, including disfigurement and impairment of basic functions, such as talking, swallowing, eating and breathing. Much recent cancer biomarker research has focused on epigenetic alterations, with particular attention paid to DNA methylation due to its relative stability and amenability to measurement. Currently, no proven screening techniques are in wide-spread use for oral &pharyngeal cancer aside from visual inspection and palpation. Use of oral rinse as a non-invasive technique for sample collection may have utility in detection of DNA methylation in oral &pharyngeal cancers and therefore has potential in biomarker-based clinical applications. Hence, this proposal seeks to apply an epigenome-wide array-based approach to oral rinse samples to identify novel DNA methylation markers of oral &pharyngeal cancer that can facilitate early diagnosis and predict disease outcome (including survival and risk of recurrence or development of a 2nd primary) using the existing population resources of a large case-control study of head and neck cancer. Further, to progress to research independence in the highly complex field of molecular cancer epidemiology, I will require additional training and experience conducting bioinformatic analyses and lab-based molecular techniques for epigenetic analysis, in particular design and conduct of pyrosequencing assays. I also need to gain key experience in the comprehensive management of an NIH funded research project in molecular cancer epidemiology. This K22 award will afford me the opportunity to obtain the necessary experience and further develop these areas through formal and informal training activities (including additional biostatistical coursework), which are crucial to my transition to he independent stage of my research career in molecular cancer epidemiology.

Public Health Relevance

This application proposes to use the resources of a large, established, population-based case-control study of head and neck cancer to identify novel biomarkers for diagnosis and outcome prediction for oral &pharyngeal cancer using a readily available, non-invasive oral rinse collection technique. Discovery and development of better biomarkers for detection and prognostication of oral &pharyngeal cancers will significantly impact public health through the reduction of morbidity and mortality that occurs as a result of this disease. The written critiques of individual reviewers are provided in essentially unedited form in this section. Please note that these critiques and criteria scores were prepared prior to the meeting and may not have been revised subsequent to any discussions at the review meeting. The Resume and Summary of Discussion section above summarizes the final opinions of the committee.

National Institute of Health (NIH)
National Cancer Institute (NCI)
Career Transition Award (K22)
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Subcommittee G - Education (NCI)
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Jakowlew, Sonia B
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University of Cincinnati
Public Health & Prev Medicine
Schools of Medicine
United States
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Langevin, Scott M; Butler, Rondi A; Eliot, Melissa et al. (2014) Novel DNA methylation targets in oral rinse samples predict survival of patients with oral squamous cell carcinoma. Oral Oncol 50:1072-80
Langevin, Scott M; Houseman, E Andres; Accomando, William P et al. (2014) Leukocyte-adjusted epigenome-wide association studies of blood from solid tumor patients. Epigenetics 9:884-95
Langevin, Scott M; Pinney, Susan M; Leung, Yuet-Kin et al. (2014) Does epigenetic drift contribute to age-related increases in breast cancer risk? Epigenomics 6:367-9
Langevin, Scott M; Christensen, Brock C (2014) Let-7 microRNA-binding-site polymorphism in the 3'UTR of KRAS and colorectal cancer outcome: a systematic review and meta-analysis. Cancer Med 3:1385-95