Upper Gastrointestinal Cancer Studies

上消化道癌症研究

• 批准号: 7288857
• 负责人: Sanford M Dawsey
• 金额: --
• 依托单位: DIVISION OF CANCER EPIDEMIOLOGY AND GENETICS
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7288857
• 关键词: Upper; Gastrointestinal; Cancer; Studies

OBJECTIVE: The objectives of this project are (1) to examine hypotheses relating to the etiology and prevention of upper gastrointestinal (UGI) cancers, and (2) to develop successful clinical strategies for the early detection and treatment of these cancers. BACKGROUND: Gastric and esophageal cancers are the second and sixth most common causes of cancer death worldwide. Both of these cancers have a very poor prognosis, largely because symptoms usually do not occur until late in the disease. Significant reduction in UGI cancer mortality will probably require development of new prevention strategies based on identification of modifiable risk factors and development of new methods to diagnose and treat more cases at earlier, more curable stages of disease. Both etiologic and early detection studies are most efficiently done in high-risk populations, so many of the studies in this project are performed in such populations. METHODS: (1) Etiologic studies: (a) China: Between 1985 and 1991, we conducted two randomized nutrition intervention trials (NIT), in Linxian, China, a county where cumulative death rates due to esophageal squamous cell carcinoma and gastric cardia cancer exceed 20%. These trials, with a combined enrollment of nearly 33,000, evaluated the effect of supplementation with several vitamin/mineral combinations on UGI cancers and found significant reductions in total mortality and gastric cancer mortality among those taking a combination of selenium, beta-carotene and vitamin E. Since 1991, we have followed the NIT participants as a cohort, and have performed nested studies evaluating the association between baseline characteristics and later development of UGI cancers. (b) Iran: We are currently conducting a case-control study (300 cases, 600 controls) of esophageal squamous cell carcinoma (ESCC) in Golestan Province, Iran, another population with high rates of ESCC. Comparing results from high-risk populations in Iran and China, which are quite distinct geographically, ethnically and culturally, should give us insight into which environmental and genetic risk factors that are most important for the development of this disease. (c) Other: We have begun preliminary studies evaluating PAH exposure in high ESCC risk populations in southern Brazil and in western Kenya. (2) Early Detection and Treatment studies: This part of the project includes four studies: (a) the Cytology Sampling Study (CSS), to develop practical and accurate primary screening tests for esophageal squamous dysplasia and early ESCC; (b) the Mucosal Staining Study (MSS), to develop methods for endoscopic localization of squamous and glandular dysplasia of the esophagus and stomach; (c) the Endoscopic Therapy Pilot Study (ETPS), to evaluate new techniques for endoscopic treatment of high-grade squamous dysplasia and early ESCC; and (d) the Chemoregression Study (CRS), to test chemoprevention strategies to reduce progression and increase regression of low-grade esophageal squamous dysplasia. PROGRESS: (1) Etiologic studies: (a) China: Recent results from nested studies in the NIT cohort have shown: (i) a strong association between low serum selenium levels and increased ESCC and gastric cardia cancer risk; (ii) no relation between serum carotenoids and risk of UGI cancers; (iii) a strong association between low serum alpha-tocopherol levels and increased ESCC risk; (iv) a strong association between low tissue zinc levels and increased ESCC risk; (v) increased risk for both cardia and non-cardia gastric cancer among subjects with positive serology for H pylori; (vi) no relation between fumonisin exposure and ESCC risk; (vii) an association between tooth loss and risk of UGI cancers; and (viii) associations between several genetic polymorphisms and risk of ESCC and/or gastric cardia cancer. (b) Iran: In the first year of accrual in the Iranian case-control study, we have enrolled 100 cases and 200 controls.

目的：该项目的目标是（1）检查与胃肠道（UGI）癌症的病因和预防有关的假设，以及（2）开发成功的临床策略，以早日检测和治疗这些癌症。背景：胃癌和食道癌是全球癌症死亡的第二和第六大最常见原因。这两种癌症的预后都很差，主要是因为症状通常直到疾病后期才发生。基于鉴定可修改的危险因素和开发新方法以诊断和治疗更多病例，在更早的疾病阶段诊断和治疗更多病例，UGI癌症死亡率的大幅降低可能需要开发新的预防策略。在高危人群中，病因学和早期检测研究都是最有效的，因此该项目中的许多研究都是在此类人群中进行的。方法：（1）病因研究：（a）中国：在1985年至1991年之间，我们在中国林克斯（Linxian）进行了两项随机营养干预试验（NIT），一个县，一个县，由于食管食管鳞状细胞癌和胃癌癌症累积死亡率超过20％。这些试验的组合结合近33,000个，评估了补充几种维生素/矿物质组合对UGI癌症的补充作用，发现总体死亡率和胃癌的总死亡率显着降低，而硒，β-胡萝卜素和维生素E的组合之间的基本研究是自1991年以来的研究，我们已经遵循了一列的参与者，并遵循了nit nitters的巢穴。 UGI癌的发展。 （b）伊朗：我们目前正在进行一项病例对照研究（300例，600例对照）的食管鳞状细胞癌（ESCC），位于伊朗戈尔斯坦省，另一个人口较高，ESCC率高。比较伊朗和中国的高风险人口的结果，这些结果在地理，种族和文化上是完全不同的，应该使我们深入了解哪些环境和遗传危险因素对于这种疾病的发展最为重要。 （c）其他：我们已经开始评估巴西南部和肯尼亚西部高ESCC风险人群中PAH暴露的初步研究。 （2）早期检测和治疗研究：该项目的这一部分包括四个研究：（a）细胞学抽样研究（CSS），以开发针对食管鳞状异常增生和早期ESCC的实用，准确的原发性筛查测试； （b）粘膜染色研究（MSS），开发了食管和胃的鳞状和腺体发育不良的内窥镜定位方法； （c）内窥镜治疗试验研究（ETP），以评估用于内窥镜治疗高级鳞状发育不良和早期ESCC的新技术； （d）化学进展研究（CRS），测试化学预防策略，以减少进展并增加低级食管鳞状发育不良的消退。进度：（1）病因学研究：（a）中国：NIT队列嵌套研究的最新结果表明：（i）低血清硒水平与ESCC和ESCC和胃Cardia癌的风险增加之间有着密切的关联； （ii）血清类胡萝卜素与UGI癌的风险之间无关； （iii）低血清α-生育酚水平与ESCC风险增加之间的密切关联； （iv）低组织锌水平与ESCC风险增加之间的密切关联； （v）幽门螺杆菌血清学阳性的受试者中心脏病和非心脏胃癌的风险增加； （vi）富莫尼菌素暴露与ESCC风险之间没有关系； （vii）牙齿癌的牙齿丧失与风险之间的关联； （viii）几种遗传多态性与ESCC和/或胃癌癌的风险之间的关联。 （b）伊朗：在伊朗案件对照研究的指控第一年，我们招募了100例病例和200例对照。