Squamous cell carcinoma of the oropharynx (SCCOP) is characterized by local tumor aggressiveness requiring morbid local-regional therapies with poor survival and high recurrence rates. Despite declining smoking prevalence, the incidence of SCCOP is stagnant and incidence is increasing in young adults. These trends may be due to the rising prevalence of oncogenic human papillomavirus (HPV) in the population. HPV+ SCCOP is a distinct epidemiologic, clinical, and molecular disease with potentially unique clinical behavior and treatment responses. Identification of those needing treatment intensification and those able to benefit from reduction of treatment intensity is critical to more effective and less morbid treatment. Oncogenic subtypes of HPV, principally type 16, are critical etiologic factors in a distinct subset of head and neck cancers, chiefly SCCOP. Inflammation/immune responses which control the HPV clearance and escape of immune surveillance may contribute to the risk and possibly the outcomes of HPV-associated SCCOP. In addition, the unique pattern of genetic profiles in HPV+ SCCOP might confound correlations with clinical outcome. Therefore, we speculate that genetic polymorphisms in the likely functional regions of these genes may pose individual difference in susceptibility to HPV infection and constitute the confounding effect on HPV-related clinical outcomes. In this case-case comparison study, the study subjects will be 300 patients with incident SCCOP retrospectively identified from an existing molecular epidemiologic study of squamous cell carcinoma of the head and neck.
The specific aims for this R03 project are: 1) to establish a database with demographic, clinical and follow-up information, genotypes of the polymorphisms, and HPV16 DNA tumor status on 300 of these SCCOP patients, 2) to assess genotypes of Inflammation/immune response related genes involved in both pro- and anti-inflammation pathways as markers of susceptibility for HPV16 association among patients with SCCOP, and 3) To determine if variants of these genes in both pro- and anti-inflammation pathways modify HPV-related clinical outcomes (recurrence and survival) of SCCOP patients. The long-term goal of this project is to use these genetic polymorphisms as surrogate markers to help identify individuals at high risk of HPV16 infection and/or at risk for poor outcomes in order to better individualize SCCOP prevention and treatment as well as improve of both survival and quality of life.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Small Research Grants (R03)
Project #
5R03CA135679-02
Application #
7643919
Study Section
Special Emphasis Panel (ZCA1-SRRB-D (M1))
Program Officer
Freedman, Andrew
Project Start
2008-07-01
Project End
2011-06-30
Budget Start
2009-07-01
Budget End
2011-06-30
Support Year
2
Fiscal Year
2009
Total Cost
$77,000
Indirect Cost
Name
University of Texas MD Anderson Cancer Center
Department
Surgery
Type
Other Domestic Higher Education
DUNS #
800772139
City
Houston
State
TX
Country
United States
Zip Code
77030
Zhang, Hua; Sturgis, Erich; Zhu, Lijun et al. (2018) The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy. Transl Oncol 11:633-638
Tao, Ye; Sturgis, Erich M; Huang, Zhigang et al. (2018) TGF?1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy. Clin Cancer Res 24:2225-2233
Tao, Ye; Sturgis, Erich M; Huang, Zhigang et al. (2018) A TGF-?1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer. Int J Cancer 143:1327-1334
Lu, Zhongming; Sturgis, Erich M; Zhu, Lijun et al. (2018) Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx. Mol Carcinog 57:361-369
Li, Yuncheng; Sturgis, Erich M; Zhu, Lijun et al. (2017) E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx. Mol Carcinog 56:1335-1343
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
Lu, Zhongming; Zhang, Hua; Tao, Ye et al. (2017) MDM4 genetic variants predict HPV16-positive tumors of patients with squamous cell carcinoma of the oropharynx. Oncotarget 8:86710-86717
Zhang, Yang; Sturgis, Erich M; Li, Yuncheng et al. (2017) Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx. Sci Rep 7:39765
Lim, Ming Yann; Dahlstrom, Kristina R; Sturgis, Erich M et al. (2016) Human papillomavirus integration pattern and demographic, clinical, and survival characteristics of patients with oropharyngeal squamous cell carcinoma. Head Neck 38:1139-44
Chen, Xingming; Sturgis, Erich M; Wang, Chengyuan et al. (2016) Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy. Oncotarget 7:35015-25

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