Phase III Study of the Effects of Selenium on Adenomas

结直肠癌（CRC）是美国癌症死亡的第二大原因。结直肠腺瘤（CRAs）是crc的前体，但大多数CRAs不会发展为crc。晚期cra，那些最有可能进展的cra，在结肠癌预防计划项目（CCPPP）中被强调。大多数cra可行内镜息肉切除术。复发性cra在既往cra患者中以每年10-15%的速度发展，并作为结直肠癌化学预防试验的终点。麦麸纤维（WBF）补充剂和熊脱氧环酸（UDCA）的CRA复发试验在早期的CCPPP资助中完成。目前是一项安慰剂对照因子设计，塞来昔布和硒（Cel/Sel）的CRA复发试验，单独或共同给药，1600名近期CRA息肉切除术后的参与者。塞来昔布是一种选择性环氧化酶(COX)- 2抑制剂，据推测其毒性低于具有同等抗neop作用的阿司匹林！astic功效。硒补充已被证明对CRC和普遍的CRAs具有继发性而非原发性的保护作用

Colorectal cancer (CRC) is the second leading cause of cancer deaths in the United States. Colorectal adenomas (CRAs) are the precursors of CRCs, but most CRAs do not progress to CRCs. Advanced CRAs, those CRAs most likely to progress, are highlighted in this Colon Cancer Prevention Program Project (CCPPP). Most CRAs are amenable to endoscopic polypectomy. Recurrent CRAs develop at a rate of 10-15% per year in patients with previous CRAs and serve as endpoints in CRC chemoprevention trials. CRA recurrence trials of a wheat bran fiber (WBF) supplement and ursodeoxychclic acid (UDCA) were completed in earlier CCPPP grants. The current is a placebo-controlled factorial-design, CRA recurrence trial of celecoxib and selenium (Cel/Sel), administered individually and together, to 1600 participants after a recent CRA polypectomy. Celecoxib, a selective cyclooxygenase (COX)- 2 inhibitor, is hypothesized to have less toxicity than aspirin with equivalent anti-neop!astic efficacy. Selenium supplementation has been shown to protect against CRC and prevalent CRAs as secondary but not primary trial endpoints. Cel/Sel randomization is stratified for concomitant low-dose aspirin (<81 mg daily) therapy RA recurrence rates by intervention group will be determined at endpoint colonoscopies performed 3 to 5 years after baseline. Cel/Sel randomization will be completed by early 2006. Resources, including hose from the WBF and UDCA trials, are essential for the conduct of CCPPP; they include clinical and risk factor data, baseline and recurrent CRA tissue, and archived plasma and DNA. By the completion of randomization of Cel/Sel trial participants in early 2006, baseline data from = 4,300 CRA patients will be available. In addition to individual effects of celecoxib and selenium, exploratory analyses of their nteraction will be conducted. As secondary objectives, the influence of single nucleotide polymorphism variations will be analyzed in six genes for which there is evidence of genotypic effect modification of the celecoxib, aspirin or selenium interventions, or their toxicities: ornithine decarboxylase, cytochrome P450 209. UDP-glucuronosyltransferase 1A6 and the GPx-1, GPx-2 and Sep15 selenoprotein genes.