Cytokine Variants as Predictors of HPV-16 Status & Outcome of Oropharyngeal Cance

细胞因子变异体作为 HPV-16 状态的预测因子

• 批准号: 7643919
• 负责人: Guojun Li
• 金额: $ 7.7万
• 依托单位: UNIVERSITY OF TX MD ANDERSON CAN CTR
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7643919
• 关键词: Anti-Inflammatory Agents; Anti-inflammatory; Behavior Therapy; Cancer Center; Case-Control Studies; Clinical; Contracts; DNA; Data; Databases; Disease; Doctor of Medicine; Epidemiologic Studies; Exhibits; Funding; Future; Genes; Genetic Polymorphism; Genetic Variation; Genotype; Goals; Head and Neck Cancer; Head and Neck Squamous Cell Carcinoma; Hereditary Disease; Human Papillomavirus; Human papilloma virus infection; Human papillomavirus 16; IL2 gene; IL4 gene; IL6 gene; Immune Response Genes; Immune response; Immunologic Surveillance; Incidence; Individual; Individual Differences; Infection; Inflammation; Inflammatory; Interleukin-10; Interleukin-13; Lead; Molecular; Mutation; Oncogenic; Oropharyngeal; Oropharyngeal Neoplasms; Oropharyngeal Squamous Cell Carcinoma; Outcome; PTGS2 gene; Pathway interactions; Patients; Pattern; Population; Predisposition; Prevalence; Prevention; Quality of life; Radiation; Recurrence; Risk; Smoke; Specimen; Squamous cell carcinoma; Staging; Study Subject; Subgroup; Surrogate Markers; Variant; base; cytokine; follow-up; genetic profiling; high risk; improved; outcome forecast; response; smoking prevalence; treatment response; trend; tumor; young adult

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 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.

描述（由申请人提供）： 口咽（SCCOP）的鳞状细胞癌的特征是局部肿瘤侵袭性，需要病态的局部区域疗法，生存率差和复发率较高。尽管吸烟率降低，但SCCOP的发病率停滞不前，年轻人的发生率正在增加。这些趋势可能是由于人群中致癌性人乳头瘤病毒（HPV）的患病率上升所致。 HPV+ SCCOP是一种独特的流行病学，临床和分子疾病，具有潜在独特的临床行为和治疗反应。鉴定需要治疗强化的人以及能够从降低治疗强度中受益的人，对于更有效和病态的治疗至关重要。 HPV的致癌亚型，主要是16型，是头颈癌（主要是SCCOP）不同子集中的关键病因学因素。控制HPV清除率和免疫监测的逃脱的炎症/免疫反应可能有助于HPV相关SCCOP的风险，并可能导致其结果。此外，HPV+ SCCOP中遗传谱的独特模式可能与临床结果相关。因此，我们推测这些基因可能功能区域的遗传多态性可能在HPV感染的易感性上构成个体差异，并构成对HPV相关临床结果的混杂作用。 在这项病例案例比较研究中，研究对象将是300例从现有的头颈鳞状细胞癌的现有分子流行病学研究中回顾性鉴定的患者。该R03项目的具体目的是：1）建立一个具有人口统计学，临床和随访信息，多态性的基因型以及300名SCCOP患者的HPV16 DNA肿瘤状态的数据库，以评估与炎症/免疫相关的基因相关的基因型，以促进和抗抗素的相关性，以评估pro-Inflymation path的基因型。 SCCOP和3）确定这些基因在促炎和抗炎途径中的变体是否修改了SCCOP患者与HPV相关的临床结果（复发和存活）。该项目的长期目标是将这些遗传多态性用作替代标志物，以帮助识别患有HPV16感染的高风险和/或患有差结果差的人，以便更好地个性化SCCOP预防和治疗，并改善生存和生活质量。