CLUE STUDIES--EVALUATING BIOMARKERS OF CARCINOGENESIS

迫切需要资源和方法来快速评估有前景的风险和疾病生物标志物的临床效用。可利用现有的标本库对有前景的血清学和遗传标记进行初步评估。拟议的研究将使用现有的基于社区的队列，对癌症结局进行随访。参与者在1974年（CLUE I）和1989年（CLUE II）捐献了血液标本。血清/血浆、红细胞和血沉棕黄层储存于-70 ℃（1989年）。作为早期检测网络的成员，我们建议从现有的队列资源（超过58，000份标本）中留出等份血清/血浆、红细胞和DNA作为网络资源。我们将通过从患有癌症的队列参与者中收集组织标本来扩大资源。我们建议在二零零一年再进行一次血液收集运动。获得40，000份血液样本，鼓励以前的CLUE参与者再次捐赠。这将提供来自多个时间点的个体样本，并扩大队列资源。为了证明快速有效地评价多种类型的生物标志物用于早期检测癌症或发展中癌症的标志物的能力，我们提出研究三种有希望的生物标志物：脂肪酸合成酶浓度（FAS），一种早期检测侵袭性形式的乳腺癌的潜在标志物; XPD基因的遗传多态性，这是非黑色素瘤皮肤癌个体中发生第二原发癌的易感性的潜在标志;以及烟草特异性亚硝胺血红蛋白加合物（TSNA），这是吸烟者患肺癌风险的潜在标志物。CLUE研究队列将提供一种快速评估潜在标志物的机制，并帮助其从实验室过渡到临床环境。队列的长期表征和具有多个样本对于确定生物标志物的有效性（灵敏度和特异性）、生物标志物随时间的变化、与癌发生的早期与晚期的关联以及评估潜伏期是有价值的。

Resources and methods to rapidly evaluate the clinical utility of promising biomarker of risk and disease are critically needed. Preliminary assessment of promising serologic and genetic markers may be performed using available specimen banks. The proposed study will use an existing community-based cohort under follow-up for cancer outcomes. Participants donated blood specimens in 1974 (CLUE I) and 1989 (CLUE II). Serum/plasma, red blood cells and buffy coats have been stored at -70 degrees Centigrade 1989. As a member of the Early Detection Network we propose to set aside alliquots serum/plasma, red blood cells and DNA from existing cohort resources (over 58,000 specimens) as a network resource. We will expand the resource by collecting tissue specimens from Cohort participants who develop cancer. We propose to conduct another blood collection campaign in the year 2001. To obtain 40,000 blood specimens, encouraging previous CLUE participants to donate again. This will provide specimens on individuals from multiple time points and expand the cohort resources. To demonstrate the ability to rapidly and efficient evaluate multiple types of biomarkers for the early detection of cancer or markers of developing cancer we propose to study three promising biomarkers: Fatty acid synthase concentrations (FAS), a potent8ial marker for the early detection of aggressive forms of breast cancer; genetic polymorphisms in the XPD gene, a potential marker of susceptibility to the development of a second primary cancer among individuals with non-melanoma skin cancer; and tobacco-specific nitrosamine hemoglobin adducts (TSNA), a potential marker of risk for the development of lung cancer among smokers. The CLUE study cohorts will provide a mechanism to rapidly assess potential markers and aid in their transition from the laboratory to the clinical setting. The long-term characterization of the cohort and having multiple specimens are valuable for determining the validity (sensitivity and specificity) of biomarkers, changes in biomarkers over time, association with early vs late stages of carcinogenesis and assessing latency periods.