SELENIUM AND LUNG CANCER RISK IN ASBESTOS WORKERS

描述：（申请人的描述）肺癌占更多的癌症 在美国，乳腺癌、前列腺癌和结肠直肠癌的死亡率 加起来 努力提高早期发现，发展成功的筛查 计划和发现有效的化学预防剂是期望的。 硒 在动物和人类中显示出作为癌症化学预防剂的前景 问题研究 硒的抗癌活性的一个假定机制是其 细胞抗氧化系统的组成部分。 接触石棉的工人 肺癌和石棉的发病率明显增加 致癌作用被认为涉及活性氧物质。 中 对石棉接触工人的横断面研究， 个体被发现有中度痰液过多（28%）， 肺癌的风险。 这一提议的主要假设是， 口服富硒酵母（200克/天）石棉接触工人 将显示肺的中间终点生物标志物的显著改善 与安慰剂相比的癌症风险;此外， 癌症将伴随着氧化细胞标志物的减少， 损害 研究设计为随机、安慰剂对照、双盲 石棉作业工人服用高硒的试验 酵母补充剂 要检查的肺癌风险标志物包括 痰液细胞学异常、支气管内化生/发育不良和细胞核异常 痰和支气管内活检标本的形态测定。 的机理 硒的作用将使用氧化细胞标志物进行研究。 损伤，包括8-羟基脱氧鸟苷（DNA损伤的标志物）， 丙二醛（脂质过氧化的标志物），和8-异甘草定F2， （脂质过氧化的标志物），在干预之前和之后。 的 一项拟议的研究将评估硒是否能有效逆转 提示肺癌风险增加的癌前病变，并阐明 硒的潜在作用机制。 因此，本研究将提供 这是进一步确立硒作为潜在的 人肺癌的化学预防剂。

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.