NUTRITIONAL PREVENTION OF CANCER

该项目的目的是建立化学预防潜力 补充人体必需的微量元素硒（Se）。这 化学预防研究项目有机会最终 证明了硒补充剂在癌症预防中的潜力， 一项随机、双盲、原发性癌症预防试验， 低饲料硒地区的美国，因为大多数美国。 人口生活在相对低硒地区（试验诊所所在地） ），该项目结果的公共卫生影响是 非常相关和重要。这次审判的结果直接 可推广至具有非黑色素瘤皮肤病史的个体 癌症;它们也可能与其他人群有关，特别是 患其他癌症风险升高的个体。这项研究可以提供 初步证据表明，补充Sc有可能减少 所有死因和癌症的死亡率以及 癌症的发病率。 本研究是一项双盲、安慰剂对照的III期癌症研究， 在非黑色素瘤皮肤癌高危人群中进行预防试验， 使用单一营养素来检验初步试验假设， 补充可降低癌症发病率和死亡率。人口 自由生活且基本健康（无黑色素瘤病史除外 皮肤癌），并参加了七个皮肤科诊所之一， 美国东部沿海平原的饲料硒地区。试验将 使用200 mcg。400 mcg。剂量的Sc以及安慰剂。现有 服用200微克的病人补助金将维持在 剂量和新患者将被随机分配至400 mcg。次给药结束的400 微克。剂量允许血浆硒水平之间的良好分离， 治疗组和安慰剂组，并提高了统计功效， 审判 试验的外部安全性监测和咨询委员会 建议将具体目标扩大到以下健康终点： 癌症发病率和死亡率。因此，具体目标是相关的 三个问题：癌症发病率，死亡率和癌症筛查。的 与癌症发病率有关的具体目标是：证明， 与安慰剂相比，补硒可显著降低 非黑色素瘤皮肤癌（特别是鳞状细胞癌）发病率 皮肤癌），所有癌症部位的组合（除了非 黑色素瘤皮肤癌），肺、前列腺和 结直肠癌，以及癌前病变的发病率， 特别是结直肠腺瘤性息肉。与死亡率有关的是 证明补硒可降低各种原因导致的死亡率 所有癌症（特别是肺癌）的死亡率 癌症）。与癌症筛查相关的具体目标是实施 癌症筛查方案，特别是结肠癌和前列腺癌 特异性抗原其他目的是评估更高剂量的硒 并建立长期安全的硒 补充。

The purpose of this project is to establish the chemopreventive potential of supplementation with the essential trace element Selenium (Se). This chemoprevention research project has the opportunity to conclusively demonstrate the cancer prevention potential of Se supplementation in a randomized double-blind primary cancer prevention trial conducted in the low forage Se region of the U.S. Because the majority of the U.S. population lives in relatively low-Se areas (where the trial's clinics are located), the public health implications of this project's results are very relevant and significant. The results of this trial are directly generalizable to those individuals with a history of non-melanoma skin cancer; they may also be relevant for other populations, especially individuals at elevated risk for other cancers. This study can provide the initial evidence that Sc supplementation has the potential to decrease both mortality from all causes of death and cancer as well as the incidence of cancers. This study is a double-blind, placebo controlled phase III cancer prevention trial in a population at high risk of non-melanoma skin cancer, using a single nutrient to test the primary trial hypothesis that Se supplementation reduces cancer incidence and mortality. The population is free-living and essentially healthy (except for a history of non-melanoma skin cancer) and attends one of seven dermatology clinics in the low forage Se area of the eastern coastal plain of the U.S. The trial will utilize 200 mcg. and 400 mcg. doses of Sc as well as a placebo. Existing patients that are on the 200 mcg. supplement will be maintained at that dose and new patients will be randomized to the 400 mcg. dose. The 400 mcg. dose allows for excellent separation of plasma Se levels between the treatment and placebo groups and enhances the statistical power of the trial. The trial's external Safety Monitoring and Advisory Committee has recommended that the specific aims be expanded to the health endpoints of cancer incidence and mortality. Therefore, the specific aims are related to three issues: cancer incidence, mortality, and cancer screening. The specific aims related to cancer incidence are: to demonstrate that, compared to the placebo, Se supplementation will significantly reduce the incidence of non-melanoma skin cancer (specifically squamous cell carcinoma of the skin), that of all cancer sites combined (except non- melanoma skin cancer), the site-specific incidence of lung, prostate, and colorectal cancer, and the incidence of preneoplastic disease, specifically colorectal adenomatous polyps. Those related to mortality are to demonstrate that Se supplementation reduces mortality from all causes of death combined and from all cancers combined (specifically lung cancer). The specific aim related to cancer screening is to implement cancer screening protocols, specifically for colon cancer and prostate specific antigen. Additional aims are to evaluate higher doses of Se supplementation and to establish the long term safety of Se supplementation.