Nutrition Intervention Trials in Linxian China

中国临县营养干预试验

• 批准号: 7733687
• 负责人: Philip Taylor
• 金额: $ 69.01万
• 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/7733687
• 关键词: Age; Beta Carotene; Blood specimen; Cancer Death Rates; Carotenoids; Categories; China; Cohort Studies; Consumption; Cytology Histology; Data Analyses; Death Rate; Dietary Intervention; Disease; Double-Blind Method; Dysplasia; End Point; Esophageal; Etiology; Food; Fumonisins; General Population; Genetic Polymorphism; Goiter; Helicobacter pylori; Human Herpesvirus 4; Human Papillomavirus; Incidence; Intervention; Intervention Studies; Intervention Trial; Lung; Malignant Neoplasms; Malignant neoplasm of esophagus; Malignant neoplasm of lung; Micronutrients; Millet; Minerals; Nitrosamines; Numbers; Nutrient; Participant; Patient Self-Report; Persons; Placebo Control; Play; Pleura; Prevention; Randomized; Rate; Risk; Role; Selenium; Selenium/vitamin E; Serologic tests; Serum; Silicon Dioxide; Specimen; Stomach; Stomach Carcinoma; Structure of nail of toe; Study of serum; Supplementation; Testing; Tissues; Tooth Loss; Trachea and Bronchus; Trauma; Vegetables; Vitamins; Zinc; alpha Tocopherol; cancer risk; carcinogenesis; esophageal cancer prevention; malignant stomach neoplasm; mortality; stomach cardia

OBJECTIVE: The primary objective of this project is to determine if supplementation with multiple vitamin-minerals reduces the incidence and mortality of esophageal cancer, gastric cancer, and total mortality. Secondary objectives are to assess supplement effects on intermediate endpoints in carcinogenesis and to examine new hypotheses relating to the etiology and prevention of esophageal cancer and gastric cancer. BACKGROUND: Probably the highest worldwide rates of esophageal cancer occur in Linxian, China where cumulative death rates to age 75 for this cancer exceed 20%. Widespread deficiencies of multiple nutrients are considered the most likely cause, but consumption of pickled vegetables, moldy foods and nitrosamines, and physical trauma from silica fragments in ingested millet may play a role. METHODS: Two double-blind, placebo-controlled randomized intervention studies were conducted to evaluate multiple vitamins/minerals in the prevention of esophageal and other cancers. The Dysplasia Trial evaluated 3,318 persons with cytologic evidence of dysplasia supplemented for 6 years, while the General Population Trial evaluated 29,584 persons supplemented for 5 1/4 years. Biologic specimens (blood, toenails, cytology and histology specimens) were collected periodically throughout the trials. PROGRESS: TRIALS - Both trials concluded in 1991, and results showed that the combination of beta-carotene/vitamin E/selenium significantly reduced total mortality, total cancer mortality, and stomach cancer incidence and mortality. Results from endoscopic and cytologic examinations suggested that multiple vitamins/minerals may decrease proliferation and enhance cytologic reversion to nondysplasia. POST-TRIAL FOLLOW-UP - Analysis of data from 10 years of post-intervention followup (through May 2001) indicate that, for the General Population Trial, the beneficial effects of the beta-carotene/vitamin E/selenium supplementation continued after termination of the intervention, and that the benefits were greater in the younger participants. None of the four factors tested influenced lung cancer death rates. ETIOLOGY STUDIES - A number of nested case-cohort studies relating baseline serum values of micronutrients, fumonisins, Helicobacter pylori, HPV, and EBV to cancer have recently been completed. Results of recent analyses have shown: (1) an especially strong association with increased risk for esophageal cancer and gastric cardia cancer among subjects with low serum selenium levels; (2) no relation of serum carotenoids with esophageal cancer or gastric cancer; (3) a strong association for low serum alpha-tocopherol levels and esophageal cancer risk; (4) a strong association between low tissue zinc levels and increased esophageal cancer risk; (5) increased risk for H pylori exposure for gastric cancer, both cardia as well as body; (5) no relation of fumonisin exposure with esophageal cancer risk; (6) an association between tooth loss and risk of esophageal cancer and gastric cancer; (7) associations between several genetic polymorphisms and risk of esophageal cancer and gastric cardia cancer; (8) increased risk of gastric noncardia cancer in persons with self-reported goiter; and (9) no relation for HPV 16, 18, or 73 serology and esophageal cancer or gastric cancer.

目的：该项目的主要目的是确定补充多种维生素矿物质是否可以降低食道癌、胃癌的发病率和死亡率以及总死亡率。次要目标是评估补充剂对致癌作用中间终点的影响，并检验与食管癌和胃癌的病因和预防相关的新假设。背景：全球食管癌发病率最高的地区可能是中国临县，该地区 75 岁以下食管癌的累计死亡率超过 20%。多种营养素的广泛缺乏被认为是最可能的原因，但食用腌菜、发霉的食物和亚硝胺，以及摄入小米中的二氧化硅碎片造成的身体创伤也可能是其中的一个原因。方法：进行了两项双盲、安慰剂对照的随机干预研究，以评估多种维生素/矿物质预防食道癌和其他癌症的作用。不典型增生试验评估了 3,318 名有不典型增生细胞学证据的人，补充了 6 年，而一般人群试验评估了 29,584 人，补充了 5 1/4 年。在整个试验过程中定期收集生物标本（血液、脚趾甲、细胞学和组织学标本）。进展：试验 - 两项试验均于 1991 年结束，结果表明 β-胡萝卜素/维生素 E/硒的组合显着降低了总死亡率、总癌症死亡率以及胃癌的发病率和死亡率。内窥镜和细胞学检查的结果表明，多种维生素/矿物质可能会减少增殖并增强细胞学向非发育不良的逆转。试验后随访——对 10 年干预后随访数据（截至 2001 年 5 月）的分析表明，对于一般人群试验而言，补充 β-胡萝卜素/维生素 E/硒的有益效果在干预结束后仍然持续存在。干预措施，并且年轻参与者的获益更大。测试的四个因素均不影响肺癌死亡率。病因学研究 - 最近完成了许多将微量营养素、伏马菌素、幽门螺杆菌、HPV 和 EBV 的基线血清值与癌症相关的巢式病例队列研究。最近的分析结果表明：（1）血清硒水平低的受试者与食道癌和贲门癌风险增加有特别强的关联； (2)血清类胡萝卜素与食管癌、胃癌无相关性； (3) 低血清α-生育酚水平与食道癌风险密切相关； (4) 低组织锌水平与食道癌风险增加之间存在密切关联； (5) 幽门螺杆菌暴露导致胃癌（包括贲门癌和胃癌）的风险增加； (5)伏马菌素暴露与食管癌风险无关； (6) 牙齿脱落与食道癌和胃癌风险之间的关联； (7)几种基因多态性与食管癌、贲门癌风险的关联； (8) 自述有甲状腺肿的人患非贲门癌的风险增加； (9) HPV 16、18 或 73 血清学与食道癌或胃癌没有关系。

项目成果

Prospective study of serum 25(OH)-vitamin D concentration and risk of oesophageal and gastric cancers.

• DOI: 10.1038/sj.bjc.6603834
• 发表时间: 2007-07-02
• 期刊: BRITISH JOURNAL OF CANCER
• 影响因子: 8.8
• 作者: Chen, W.;Dawsey, S. M.;Qiao, Y-L;Mark, S. D.;Dong, Z-W;Taylor, P. R.;Zhao, P.;Abnet, C. C.
• 通讯作者: Abnet, C. C.

Self-reported goiter is associated with a significantly increased risk of gastric noncardia adenocarcinoma in a large population-based Chinese cohort.

在一个大型中国人群队列中，自我报告的甲状腺肿与胃非贲门腺癌的风险显着增加相关。

• DOI: 10.1002/ijc.21993
• 发表时间: 2006
• 期刊: International journal of cancer. Journal international du cancer
• 作者: Abnet,ChristianC;Fan,Jin-Hu;Kamangar,Farin;Sun,Xiu-Di;Taylor,PhilipR;Ren,Jian-Song;Mark,StevenD;Zhao,Ping;FraumeniJr,JosephF;Qiao,You-Lin;Dawsey,SanfordM
• 通讯作者: Dawsey,SanfordM