Biomarkers of UC Tumorigenesis

描述（由申请人提供）：持续时间超过8年的广泛溃疡性结肠炎（UC）患者患结直肠癌的风险增加，每年结肠炎的风险约为1%。因此，患有20年UC的患者将有大约20%的肿瘤风险。目前所有长期UC患者的实践标准是对结直肠癌进行终身结肠镜监测。有关监测的主要问题包括：1)结肠表面积大；2)：在这个大范围内的任何地方都可能出现发育不良，并且经常不产生内窥镜下可见的病变；3)炎症性肠病中异常增生的诊断是一种主观解释，需要经验丰富的病理学家才能达到最佳准确性；在美国，近50万人患有UC；这些患者的癌症监测是昂贵的、耗时的、复发的（每1-2年）和终身的。本研究的长期目标是更好地了解（UC）肿瘤进展的分子机制，并利用这些知识改善对可治愈癌症及其前体的监测。

DESCRIPTION (provided by applicant): Patients with extensive ulcerative colitis (UC) of more than 8 years duration have an increased risk of colorectal cancer which approximates 1% per year of colitis. Thus, a patient who has 20 years of UC will have a neoplastic risk that approximates 20%. The current standard of practice in all patients with longstanding UC is to perform life-long colonoscopic surveillance for colorectal cancer. There are major problems regarding surveillance including: 1) the large surface area of the colon; 2): dysplasia may arise anywhere within this large area and frequently produces no endoscopically visible lesion; 3) the diagnosis of dysplasia in inflammatory, bowel disease is a subjective interpretation and requires an experienced pathologist for optimum accuracy; Nearly half of a million people have UC in the United States; cancer surveillance in these patients is costly, time intensive, recurrent (every 1-2 years), and life-long. The long term objectives of this research are to better understand the molecular mechanisms of neoplastic progression in (UC) and to use this knowledge for improved surveillance of curable cancer and its precursors. Our previous studies have made it clear that even the non-dysplastic mucosa is genetically abnormal in UC patients who have neoplasia. In fact, the entire colon appears to show genetic instability in UC patients with cancer or dysplasia. We believe that this information is central to understanding the underlying causes of neoplastic progression and for developing new methods for cancer surveillance of UC patients. Such new methods could change the face of clinical care for these patients and their providers. Our goals remain to better understand the genomic changes during carcinogenesis in UC, and to use this knowledge to find early markers that will enable us to concentrate our surveillance efforts on those patients most likely to benefit from them. Both of these goals will help provide the underpinnings for development of cancer prevention strategies in the future.