This proposal is built upon the epidemiologic and molecular genetic findings from our 20-year experience in translational research in oral premalignant lesions (OPLs), a hallmark of oral cancer development. Although the etiology of OPLs is not fully understood, these lesions are often associated with tobacco and alcohol exposures;however, it is unclear why only a fraction of exposed individuals with OPL subsequently develop oral cancer. We have previously shown that OPL patients with certain genetic backgrounds are more susceptible to developing oral cancer, and that certain molecular abnormalities that present in OPL target tissues predict a higher rate of malignant transformation of these lesions, independent of clinicopathologic parameters. These predictive markers include OPL histology and the combined biomarker scores of chromosomal polysomy, p53 protein expression, and loss of heterozygosity (LOH) at 3p and 9p in OPL tissues. We have demonstrated a successful strategy for comprehensive cancer risk assessment in OPL patients by combining conventional medical/demographic variables and a panel of biomarkers;however, all of these studies have utilized small sample sizes. We propose to extend our studies by utilizing the largest available resource of OPL specimens that allows us the unprecedented opportunity to study 350 patients with OPLs, prospectively followed, to parallel our investigation of genetic markers in surrogate and target tissues, critical molecular candidates, and global genetic aberrations and expression profiles to identify predictors of oral cancer risk in these patients. Using this unique resource, we will integrate clinical, epidemiologic, and genetic data to build a quantitative risk assessment model for oral cancer development.
Our Specific Aims i nclude: 1) Assess susceptibility markers in surrogate tissue (lymphocytes);2) Assess global genomic and transcriptomic abnormalities as well as critical candidate molecules in OPL target tissues;and 3) Complete comprehensive analyses of data from clinical, epidemiologic, surrogate-target tissue, genotype-phenotype, global-candidate biomarker panels with patients'clinical outcomes to build a risk assessment model for oral cancer development. The identification of subgroups of OPL patients at higher risk for oral cancer development will allow the development of individually tailored, mechanism-based chemopreventive interventions and strategies for more effective screening and treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center (P50)
Project #
5P50CA097007-10
Application #
8380162
Study Section
Special Emphasis Panel (ZCA1-GRB-I)
Project Start
Project End
2014-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
10
Fiscal Year
2012
Total Cost
$380,548
Indirect Cost
$120,357
Name
University of Texas MD Anderson Cancer Center
Department
Type
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Li, Rui; Ding, Chunyong; Zhang, Jun et al. (2017) Modulation of Bax and mTOR for Cancer Therapeutics. Cancer Res 77:3001-3012
Quinlan-Davidson, Sean R; Mohamed, Abdallah S R; Myers, Jeffrey N et al. (2017) Outcomes of oral cavity cancer patients treated with surgery followed by postoperative intensity modulated radiation therapy. Oral Oncol 72:90-97
Cardenas, Carlos E; Mohamed, Abdallah S R; Tao, Randa et al. (2017) Prospective Qualitative and Quantitative Analysis of Real-Time Peer Review Quality Assurance Rounds Incorporating Direct Physical Examination for Head and Neck Cancer Radiation Therapy. Int J Radiat Oncol Biol Phys 98:532-540
Rosenthal, David I; Mohamed, Abdallah S R; Garden, Adam S et al. (2017) Final Report of a Prospective Randomized Trial to Evaluate the Dose-Response Relationship for Postoperative Radiation Therapy and Pathologic Risk Groups in Patients With Head and Neck Cancer. Int J Radiat Oncol Biol Phys 98:1002-1011
MD Anderson Head and Neck Cancer Symptom Working Group (2017) Dose-volume correlates of mandibular osteoradionecrosis in Oropharynx cancer patients receiving intensity-modulated radiotherapy: Results from a case-matched comparison. Radiother Oncol 124:232-239
Liu, Zhensheng; Liu, Hongliang; Han, Peng et al. (2017) Apoptotic capacity and risk of squamous cell carcinoma of the head and neck. Eur J Cancer 72:166-176
Singh, Tarjinder; Walters, James T R; Johnstone, Mandy et al. (2017) The contribution of rare variants to risk of schizophrenia in individuals with and without intellectual disability. Nat Genet 49:1167-1173
MICCAI/M.D. Anderson Cancer Center Head and Neck Quantitative Imaging Working Group (2017) Matched computed tomography segmentation and demographic data for oropharyngeal cancer radiomics challenges. Sci Data 4:170077
Li, Jie; Mitani, Yohitsugu; Rao, Pulivarthi H et al. (2017) Establishment and genomic characterization of primary salivary duct carcinoma cell line. Oral Oncol 69:108-114
Zhu, Lijun; Sturgis, Erich M; Zhang, Hua et al. (2017) Genetic variants in microRNA-binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx. Int J Cancer 141:1355-1364

Showing the most recent 10 out of 342 publications