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应用。可利用标本库对有希望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社区队列，对癌症结果进行随访。参与者在1974年（CLUE I）和1989年（CLUE II）捐献了血液标本。1989年，血清/血浆、红细胞和棕黄色被保存在-70摄氏度。作为早期检测网络的成员，我们建议从现有队列资源（超过58,000个标本）中留出血小板、血清/血浆、红细胞和DNA作为网络资源。我们将通过收集患有癌症的队列参与者的组织标本来扩大资源。我们建议在二零零一年再进行一次采血运动。收集40,000份血液样本，鼓励以前的CLUE参与者再次献血。这将提供来自多个时间点的个体标本，并扩大队列资源。为了证明快速有效地评估多种类型的生物标志物用于早期检测癌症或发展中的癌症标志物的能力，我们建议研究三种有前景的生物标志物：脂肪酸合成酶浓度（FAS），一种早期检测侵袭性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患者患第二原发性癌症的潜在易感性标志；以及烟草特异性亚硝胺血红蛋白加合物（TSNA），这是吸烟者患肺癌的潜在风险标志。CLUE研究队列将提供一种快速评估潜在标志物的机制，并帮助它们从实验室过渡到临床环境。队列的长期特征和具有多个标本对于确定生物标志物的有效性（敏感性和特异性），生物标志物随时间的变化，与早期和晚期癌变的关联以及评估潜伏期具有价值。

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.