CLINICAL AND EPIDEMIOLOGIC CENTER FOR BIOMARKERS OF UPPE

我们建议建立一个临床和流行病学中心，专注于上呼吸消化道（UADT）病变的生物标志物，这是研究风险标志物，早期检测和干预反应的优秀模型。我们将建立在资助组间化学预防试验和流行病学研究的基础上，这些研究涵盖了UADT疾病的连续性，从癌前病变到第二原发肿瘤的风险。我们建议：1.临床资源：我们已经批准了方案，跟踪系统，积极的后续行动和大量的初步数据的受试者参加化学预防和流行病学UADT研究。我们可以通过我们多样化的患者人群、流行病学研究的比较对象以及我们自己中心的癌症遗传学网络的基础设施来扩展资源。2.生物标志物资源：整合了一组全面的风险生物标志物，早期检测和对生殖系DNA，癌前病变，邻近正常上皮和浸润性癌症中表达的干预反应。这些包括组织标记物-例如，基因组不稳定性标志物（染色体多体性，9 p21、3 p14和17 p的洛）、增殖、p53、细胞周期蛋白D1、EGFR和RAR表达-和风险标志物-例如，表型（体外淋巴细胞测定）和基因型（代谢多态性）。3. 相互关联的研究项目（3），以评估有前途的候选遗传和表型细胞和分子生物标志物，用于表征该领域和多步骤UADT肿瘤发生过程;并评估风险，早期检测和早期和晚期恶性肿瘤病变以及UADT的首次和多种癌症的反应。4.用于结合生物标志物数据的统计方法;用于评估基因型/表型和替代/靶组织标志物相关性;以及开发第二原发性肿瘤的风险评估模型。5.烟草诱导的上皮癌（如膀胱癌）生物标志物的开发项目。6.与工业界合作，验证微阵列技术，对一系列多态性代谢易感基因进行大规模基因分型。7.与膀胱癌生物标志物开发基金（B）的合作。Czerniak，P.I.）总的来说，我们在烟草致癌易感性、化学预防干预和生物标志物分析方面的基础、临床、转化和流行病学研究方面有着长期而成功的记录。因此，我们有我们拟议研究的相关主题;我们有令人信服的初步数据;我们有必要的专业知识和组织结构，以取得最大的成功。调查小组是多学科的，将能够及时和灵活地对网络的指示作出反应，并加强和扩大网络的研究能力。

We propose to create a Clinical and Epidemiologic Center focused on Biomarkers for Upper Aerodigestive Tract (UADT) Lesions, an Excellent model for studying markers of risk, early detection and response to intervention. We will build upon funded intergroup chemopreventive trials and epidemiologic studies that span the continuum of UADT disease, from pre-malignant lesions to risk of second primary tumors. We propose: 1. A Clinical Resource: We have approved protocols, tracking systems, active follow-up and substantial preliminary data on subjects enrolled in chemoprevention and epidemiologic UADT studies. We can expand the resource with our diverse patient population, comparison subjects from epidemiologic studies, and the infrastructure from our own center's Cancer Genetics Network. 2. Biomarker Resource: Integration of a comprehensive panel of biomarkers of risk, early detection and response to intervention expressed in germline DNA, premalignant lesions, adjacent normal epithelium, and invasive cancers. These include tissue markers-e.g., genomic instability markers (chromosomal polysomy, LOH of 9p21, 3p14, and 17p), proliferation, p53, cyclin D1, EGFR, and RAR expression- and risk markers-e.g., phenotypic (in vitro lymphocyte assays) and genotypic (metabolic polymorphisms). 3. Inter-related research projects (3) to evaluate promising candidate genetic and phenotypic cellular and molecular biomarkers useful for characterizing the field and the multi-step UADT tumorigenesis process; and for assessment of risk, early detection, and response in early and advanced pore-malignant lesions and first and multiple cancers of the UADT. 4. Statistical methodologies for combining biomarker data; for assessing genotype/phenotype and surrogate/target tissue marker correlations; and to develop a risk assessment model for second primary tumors. 5. Developmental projects in biomarkers for tobacco-induced epithelial cancers e.g. bladder cancer. 6. Collaboration with industry to validate microarray technology to perform large scale genotyping of a range of polymorphic metabolic susceptibility genes. 7. Collaboration with a pending Biomarker Development Grant on Bladder Cancer (B. Czerniak, P.I.) Collectively, we have a long and successful track record of basic, clinical, translational, and epidemiologic research in susceptibility to tobacco carcinogenesis, in chemopreventive interventions, and in biomarker analysis. Thus, we have the relevant subjects for our proposed studies; we have compelling preliminary data; and we have the necessary expertise and organization structure to maximize success. The team of investigators is multi-disciplinary and will be able to respond in a timely and flexible manner to network directives, and to enhance and augment the network's research capabilities.