PROGNOSTIC & PREDICTIVE FACTORS IN OUTCOME OF PATIENTS WITH COLORECTAL CANCER:

现在有证据表明，结直肠癌的分子特征可以影响预后并预测对治疗的反应。这项拟议的研究的动机是相信更好的预后和预测因素的信息将有可能定制治疗，以最大限度地提高效益和降低成本，并希望了解结直肠癌死亡率的种族差异。本研究的具体目的是：（1）确定哪些患者、治疗和结肠肿瘤的分子特征是预后的独立预测因素。(2)确定肿瘤特征和治疗因素之间的相互作用以及对治疗的反应。(3)为了确定肿瘤特征的种族差异是否是导致 黑人结直肠癌的5年生存率更低。这项拟议的研究将利用在一项前瞻性、基于人群的研究中收集的数据，该研究将获得关于患者特征、治疗、结局以及从北卡罗来纳州22个县的多样化、混合种族随机抽取的1000名新诊断的结直肠癌患者（600名白人和400名黑人）的肿瘤块的非常详细的信息。具体的分子特征将包括涉及细胞周期、细胞生长、凋亡和细胞粘附的基因的蛋白产物的表达，例如p53、k-ras、钙结合、细胞粘附和细胞粘附。 蛋白S100 A4、细胞周期蛋白D、IGFII、TGF-β RII、MLH 1和MSH 2。将使用多肿瘤组织阵列块评价这些标志物。此外，该研究将使用来自显微切割块的DNA来评价染色体2 p、5 q、17 p和18 q上的异质性丢失（洛），并将使用BAT 25、BAT 26和D17 S250、D5 S346、D2 S123评估微卫星不稳定性（MSI）。

There is now evidence that molecular characteristics of colorectal cancer can influence prognosis and predict response to therapy. The proposed study is motivated by the belief that better information on prognostic and predictive factors will make it possible to tailor therapy to maximize benefits and reduce cost, and by a desire to understand racial disparities in colorectal cancer mortality. The specific aims of the study are: (1) To determine which patient, treatment and molecular characteristics of colon tumors are independent predictors of prognosis. (2) To determine interactions between tumor characteristics and treatment factors and the response to therapy. (3) To determine whether racial differences in tumor characteristics are responsible for the worse 5-year survival in colorectal cancer in blacks. The proposed study will take advantage of data collected in a prospective, population-based study that will obtain exceptionally detailed information on patient characteristics, treatment, outcomes as well as tumor blocks on 1000 newly-diagnosed colorectal cancer patients (600 whites and 400 blacks) drawn at random from a diverse, mixed-race, 22 county area in North Carolina. The specific molecular characteristics will include expression of protein products of genes involved in cell cycle, cell growth, apoptosis, and cellular adhesion such as p53, k-ras, calcium binding protein S 100A4, cyclin D, IGFII, TGF-betaRII, MLH1, and MSH2. These markers will be evaluated using multitumor tissue array blocks. In addition, the study will use DNA from microdissected blocks to evaluate loss of heterogeneity (LOH) on chromosomes 2p, 5q, 17p and 18q, and will assess microsatellite instability (MSI) using BAT25, BAT26 and D17S250, D5S346, D2S123.