SELENIUM AND LUNG CANCER RISK IN ASBESTOS WORKERS

描述：(应聘者描述)肺癌占癌症的比例更高 美国的死亡率高于乳腺癌、前列腺癌和结直肠癌 加在一起。努力改进早期发现，开发成功的筛查 计划和寻找有效的化学预防药物是可取的。硒 在动物和人类身上显示出作为癌症化学预防药物的前景 学习。硒的抗癌活性的一个可能机制是其 是细胞抗氧化系统中不可或缺的一部分。接触石棉的工人已经 众所周知，肺癌和石棉的发病率有所上升 癌症的发生被认为涉及到活性氧物种。在一个 石棉接触工人的横断面研究，大量 个人被发现有中度的痰非典型性(28%)，这是一种标志 有患肺癌的风险。这项提议的主要假设是 石棉接触者口服富硒酵母(200克/天) 将显示肺的中间终点生物标志物有显著改善 与安慰剂相比的癌症风险；此外，肺部标志物的变化 癌症将伴随着氧化细胞标志物的减少 损坏。研究设计为随机、安慰剂对照、双盲 石棉作业工人使用高硒的试验研究 酵母补充剂。需要检查的肺癌风险标志包括 痰细胞异型性、支气管化生/异型增生和核 痰和支气管内膜活检标本的形态计量学。它的作用机制 将使用氧化细胞标志物来研究硒的作用 损伤，包括8-羟基脱氧鸟苷(DNA损伤的标志)， 丙二醛(脂质过氧化的标志)和8-异前列腺素F2， (脂质过氧化的标记物)，干预前后。这个 拟议的研究将评估硒是否有效逆转 癌前病变提示肺癌风险增加并阐明 硒的潜在作用机制。因此，这项研究将提供 进一步确立硒作为潜在能源的关键基础 人类肺癌的化学预防药物。

DESCRIPTION: (Applicant's Description) Lung cancer accounts for more cancer deaths in the United States than breast, prostate and colorectal cancer combined. Efforts to improve early detection, develop successful screening programs and find effective chemopreventive agents are desirable. Selenium has shown promise as a cancer chemopreventive agent in animal and human studies. A putative mechanism of selenium's anticarcinogenic activity is its integral part in cellular antioxidant systems. Asbestos-exposed workers have a well established increased incidence of lung cancer, and asbestos carcinogenesis is thought to involve activated oxygen species. In a cross-sectional study of asbestos-exposed workers, a large number of individuals were found to have moderate sputum atypia (28 percent), a marker of lung cancer risk. The major hypothesis of this proposal is that asbestos-exposed workers treated with oral selenium-rich yeast (200gg/day) will show significant improvement in intermediate end-point biomarkers of lung cancer risk compared to placebo; and furthermore, changes in markers of lung cancer will be accompanied by decreases in markers of oxidative cellular damage. The study design is a randomized, placebo-controlled, double blind trial of asbestos-exposed construction trades workers using high selenium yeast supplementation. Markers of lung cancer risk to be examined include sputum cytologic atypia, endobronchial metaplasia/dysplasia, and nuclear morphometry of sputum and endobronchial biopsy specimens. The mechanism of action of selenium will be investigated using markers of oxidative cellular damage, including 8-hydroxydeoxyguanosine (a marker of DNA damage), malondialdehyde (a marker of lipid peroxidation), and 8-iso-prostaglandine F2, (a marker of lipid peroxidation), before and after the intervention. The proposed study will assess whether selenium is effective in reversing premalignant lesions indicative of increased lung cancer risk and elucidate potential mechanisms of action of selenium. As such, this study will provide a critical foundation to further establish selenium as a potential chemopreventive agent for human lung cancer.