Selenium and colorectal adenomas and adenocarcinomas

硒与结直肠腺瘤和腺癌

• 批准号: 6619091
• 负责人: ALEXANDRA E CONNELLY
• 金额: $ 7.28万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-05-01 至 2005-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6619091
• 关键词: adenocarcinoma; adenoma; adenomatous polyps; apoptosis; atomic absorption spectrometry; biopsy; cancer risk; chemoprevention; clinical research; colorectal neoplasms; dietary trace element; human data; human tissue; intestinal mucosa; neoplasm /cancer epidemiology; nutrition aspect of cancer; nutrition related tag; pathology; rectum /anus; selenium; serology /serodiagnosis

DESCRIPTION (provided by applicant): Colorectal cancer is the second leading cause of cancer mortality in the United States, with an estimated 56,700 deaths in 2001. Most colorectal adenocarcinomas arise from benign, neoplastic adenomatous polyps. Because colorectal cancer has an identifiable precursor lesion (adenomatous polyps), a unique opportunity for early detection and intervention exists if modifiable risk factors for polyps can be identified. Variations in incidence of colorectal cancer with respect to geography and migration suggest an important environmental component to colorectal cancer risk. Selenium, an essential trace element found in cereals, wheat, dairy products, meat and fish, may prevent carcinogenesis through a number of biochemical pathways. One way that selenium might reduce cancer risk is by increasing apoptosis, or programmed cell death. This process provides a mechanism to remove damaged cells, which decreases the chance that abnormal cells will proliferate and develop into malignancies. Clinical trial data suggest a strong protective effect of selenium on cancer incidence; however, results from observational studies are inconclusive. Many of the case-control studies of selenium and colon cancer did not exclude participants with advanced disease, making it difficult to draw a conclusion given the impact that advanced disease and cancer treatment have on selenium levels in the body. Very few studies have addressed the association between selenium and colorectal adenomas and all studies that have were very small. Finally, no epidemiologic studies have assessed the potential biological pathway through apoptosis. The proposed study will make use of existing biological samples from two large studies to investigate the relation between serum selenium and early stage colorectal adenocarcinoma, in addition to its precursor lesion (adenomatous polyps). Most notably, we propose to investigate the biologic mechanism of apoptosis, which has not been previously evaluated in a human population. This research is of public health importance because selenium is a potential chemopreventive agent for colorectal cancer.

描述（由申请人提供）： 结直肠癌是美国癌症死亡率的第二大原因，估计在2001年死亡56,700例。大多数结直肠腺癌来自良性，肿瘤，肿瘤腺瘤息肉。由于结直肠癌具有可识别的前体病变（腺瘤息肉），因此如果可以识别出可修改的息肉因素，则存在一个独特的早期检测和干预机会。关于地理和迁移，大肠癌发生率的变化表明了结直肠癌风险的重要环境成分。硒是在谷物，小麦，乳制品，肉类和鱼类中发现的必不可少的痕量元素，可以通过多种生化途径来防止致癌作用。硒可能降低癌症风险的一种方法是增加凋亡或程序性细胞死亡。该过程提供了去除受损细胞的机制，这减少了异常细胞会增殖并发展为恶性肿瘤的机会。临床试验数据表明，硒对癌症发病率的强烈保护作用。但是，观察性研究的结果尚无定论。许多对硒和结肠癌的病例对照研究并未排除患有晚期疾病的参与者，因此很难得出结论，鉴于晚期疾病和癌症治疗对体内硒水平的影响。很少有研究涉及硒与结直肠腺瘤之间的关联以及所有非常小的研究。最后，没有流行病学研究评估了细胞凋亡的潜在生物学途径。拟议的研究还将利用来自两项大型研究的现有生物样品，以研究血清硒与早期结直肠腺癌之间的关系，除了其前体病变（腺瘤息肉）。最值得注意的是，我们建议研究细胞凋亡的生物学机制，该机制以前尚未在人口中进行评估。这项研究具有公共健康的重要性，因为硒是结直肠癌的潜在化学预防剂。