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Grant Details

Grant Number: 5R03CA186261-02 Interpret this number
Primary Investigator: Li, Guojun
Organization: University Of Tx Md Anderson Can Ctr
Project Title: Inflammatory Response Mirnas Predict HPV-Associated Oropharyngeal Cancer Outcome
Fiscal Year: 2016
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Abstract

¿ DESCRIPTION (provided by applicant): 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 increasing, particularly in young adults. These trends may be due to the rising prevalence of oncogenic human papillomavirus (HPV) in the population. HPV-positive [(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 are critical etiologic factors in a distinct subset of head and neck cancers, chiefly SCCOP. Inflammatory response miRNAs which control the HPV clearance and escape of immune surveillance may contribute to HPV(+) tumors and related outcomes of SCCOP. In addition, miRNAs in human serum hold a great potential for serum-based biomarker research. Thus, serum expression profiles of inflammatory response miRNAs before treatment may affect tumor HPV status and related outcomes of SCCOP patients; and exploitation of such associations may help develop clinically relevant non-tumor-based biomarkers for HPV- associated SCCOP patients. In this study, the study subjects will be 600 patients with incident SCCOP identified from an existing molecular epidemiologic study of squamous cell carcinoma of the head and neck. The specific aims for this R03 project are: Aim 1: To assess if serum expression profiles of selected inflammatory/immune response miRNAs before treatment are markers of tumor HPV status among the 600 SCCOP patients. We will determine serum expression of those selected miRNAs before treatment by using the miScript miRNA PCR arrays method and Aim 2: To determine if certain serum expression profiles of above miRNAs before treatment as blood-based and non-tumor predictors of clinical outcomes of HPV(+) SCCOP patients including disease-specific survival, disease-free survival, and overall survival among 600 SCCOP patients treated and followed at U.T. MDACC. By knowing the tumor HPV status and identifying novel prognostic biomarkers of HPV-associated SCCOP patients, physicians can effectively tailor treatment, screening, and follow-up strategies for an improved survival and a better quality of life as well as greatly enhanced secondary cancer prevention.

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Publications

A genetic variant within MDM4 3'UTR miRNA binding site is associated with HPV16-positive tumors and survival of oropharyngeal cancer.
Authors: Zhang Y. , Sturgis E.M. , Wei P. , Liu H. , Wang Z. , Ma Y. , Liu C. , Gu K.J. , Wei Q. , Li G. .
Source: Molecular carcinogenesis, 2019-09-12; , .
EPub date: 2019-09-12.
PMID: 31513313
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A TGF-β1 genetic variant at the miRNA187 binding site significantly modifies risk of HPV16-associated oropharyngeal cancer.
Authors: Tao Y. , Sturgis E.M. , Huang Z. , Sun Y. , Dahlstrom K.R. , Wei Q. , Li G. .
Source: International journal of cancer, 2018-09-15; 143(6), p. 1327-1334.
EPub date: 2018-05-02.
PMID: 29663347
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The Modifying Effect of a Functional Variant at the miRNA Binding Site in E2F1 Gene on Recurrence of Oropharyngeal Cancer Patients with Definitive Radiotherapy.
Authors: Zhang H. , Sturgis E. , Zhu L. , Lu Z. , Tao Y. , Zheng H. , Li G. .
Source: Translational oncology, 2018 Jun; 11(3), p. 633-638.
EPub date: 2018-03-22.
PMID: 29574328
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TGFβ1 Genetic Variants Predict Clinical Outcomes of HPV-Positive Oropharyngeal Cancer Patients after Definitive Radiotherapy.
Authors: Tao Y. , Sturgis E.M. , Huang Z. , Wang Y. , Wei P. , Wang J.R. , Wei Q. , Li G. .
Source: Clinical cancer research : an official journal of the American Association for Cancer Research, 2018-05-01; 24(9), p. 2225-2233.
EPub date: 2018-02-20.
PMID: 29463556
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MDM4 genetic variants predict HPV16-positive tumors of patients with squamous cell carcinoma of the oropharynx.
Authors: Lu Z. , Zhang H. , Tao Y. , Li X. , Li G. .
Source: Oncotarget, 2017-10-17; 8(49), p. 86710-86717.
EPub date: 2017-09-30.
PMID: 29156829
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Mouse double minute 4 variants modify susceptibility to risk of recurrence in patients with squamous cell carcinoma of the oropharynx.
Authors: Lu Z. , Sturgis E.M. , Zhu L. , Zhang H. , Tao Y. , Wei P. , Wei Q. , Li G. .
Source: Molecular carcinogenesis, 2018 03; 57(3), p. 361-369.
EPub date: 2017-11-13.
PMID: 29073727
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Genetic variants in microRNA-binding sites of DNA repair genes as predictors of recurrence in patients with squamous cell carcinoma of the oropharynx.
Authors: Zhu L. , Sturgis E.M. , Zhang H. , Lu Z. , Tao Y. , Wei Q. , Li G. .
Source: International journal of cancer, 2017-10-01; 141(7), p. 1355-1364.
EPub date: 2017-07-07.
PMID: 28646528
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Association between miRNA-binding site polymorphisms in double-strand break repair genes and risk of recurrence in patients with squamous cell carcinomas of the non-oropharynx.
Authors: Zhu L. , Sturgis E.M. , Lu Z. , Zhang H. , Wei P. , Wei Q. , Li G. .
Source: Carcinogenesis, 2017-04-01; 38(4), p. 432-438.
PMID: 28334093
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Modifying effect of mouse double minute-2 promoter variants on risk of recurrence for patients with squamous cell carcinoma of oropharynx.
Authors: Zhang Y. , Sturgis E.M. , Li Y. , Wei Q. , Huang Z. , Li G. .
Source: Scientific reports, 2017-01-03; 7, p. 39765.
EPub date: 2017-01-03.
PMID: 28045062
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E2F transcription factor 2 variants as predictive biomarkers for recurrence risk in patients with squamous cell carcinoma of the oropharynx.
Authors: Li Y. , Sturgis E.M. , Zhu L. , Cao X. , Wei Q. , Zhang H. , Li G. .
Source: Molecular carcinogenesis, 2017 04; 56(4), p. 1335-1343.
EPub date: 2017-01-02.
PMID: 27864908
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Significance of microRNA-related variants in susceptibility to recurrence of oropharyngeal cancer patients after definitive radiotherapy.
Authors: Chen X. , Sturgis E.M. , Wang C. , Cao X. , Li Y. , Wei Q. , Li G. .
Source: Oncotarget, 2016-06-07; 7(23), p. 35015-25.
PMID: 27145460
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Apoptotic variants as predictors of risk of oropharyngeal cancer recurrence after definitive radiotherapy.
Authors: Zhang F. , Sturgis E.M. , Sun Y. , Zhang Y. , Wei Q. , Zhang C. , Zheng H. , Li G. .
Source: International journal of cancer, 2015-11-15; 137(10), p. 2454-61.
EPub date: 2015-07-27.
PMID: 25976983
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A functional variant at miRNA-122 binding site in IL-1α 3' UTR predicts risk and HPV-positive tumours of oropharyngeal cancer.
Authors: Zhang Y. , Sturgis E.M. , Sun Y. , Sun C. , Wei Q. , Huang Z. , Li G. .
Source: European journal of cancer (Oxford, England : 1990), 2015 Jul; 51(11), p. 1415-23.
EPub date: 2015-05-14.
PMID: 25981582
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