The primary objective of this project is to determine if supplementation with multiple vitamins/minerals reduces the incidence and mortality of esophageal, stomach or other cancers. Secondary objectives are to examine new hypotheses relating to the etiology and prevention of upper gastrointestinal cancers. BACKGROUND: The highest rates of esophageal cancer in the world occur in Linxian, China, where cumulative death rates for this cancer to age 75 exceed 20%. Widespread deficiencies of multiple nutrients are considered the most likely cause, but consumption of pickled vegetables and moldy foods and exposure to nitrosamines and polycyclic aromatic hydrocarbons may also play a role. METHODS: We have conducted two randomized, double-blind, placebo-controlled intervention studies to evaluate supplementation with multiple vitamins/minerals as a prevention strategy for esophageal, stomach 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. Since the end of the intervention period, the participants in both trials have been followed as a cohort. PROGRESS: 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. Analysis of data from 10 years of post-intervention follow-up (through May 2001) is in progress. A number of cohort and case-cohort studies relating baseline questionnaire variables, serum analytes and tissue analytes to later development of cancer have recently been completed. Results have shown: (1) a strong association between low serum selenium levels and increased ESCC and gastric cardia cancer risk; (2) no relation between serum carotenoids and risk of upper GI cancers; (3) a strong association between low serum alpha-tocopherol levels and increased ESCC risk; (4) a strong association between low tissue zinc levels and increased ESCC risk; (5) increased risk for both cardia and non-cardia gastric cancer among subjects with positive serology for H pylori; (6) no relation between fumonisin exposure and ESCC risk; (7) an association between tooth loss and risk of upper GI cancers; and (8) associations between several genetic polymorphisms and risk of ESCC and/or gastric cardia cancer.

Agency
National Institute of Health (NIH)
Institute
Division of Basic Sciences - NCI (NCI)
Type
Intramural Research (Z01)
Project #
1Z01BC010576-01
Application #
7062337
Study Section
(CPSB)
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2004
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Abnet, Christian C; Lai, Barry; Qiao, You-Lin et al. (2005) Zinc concentration in esophageal biopsy specimens measured by x-ray fluorescence and esophageal cancer risk. J Natl Cancer Inst 97:301-6
Abnet, Christian C; Qiao, You-Lin; Dawsey, Sanford M et al. (2005) Tooth loss is associated with increased risk of total death and death from upper gastrointestinal cancer, heart disease, and stroke in a Chinese population-based cohort. Int J Epidemiol 34:467-74
Wei, Wen-Qiang; Abnet, Christian C; Qiao, You-Lin et al. (2004) Prospective study of serum selenium concentrations and esophageal and gastric cardia cancer, heart disease, stroke, and total death. Am J Clin Nutr 79:80-5
Savage, Sharon A; Abnet, Christian C; Mark, Steven D et al. (2004) Variants of the IL8 and IL8RB genes and risk for gastric cardia adenocarcinoma and esophageal squamous cell carcinoma. Cancer Epidemiol Biomarkers Prev 13:2251-7
Stolzenberg-Solomon, Rachael Z; Qiao, You-Lin; Abnet, Christian C et al. (2003) Esophageal and gastric cardia cancer risk and folate- and vitamin B(12)-related polymorphisms in Linxian, China. Cancer Epidemiol Biomarkers Prev 12:1222-6
Abnet, Christian C; Qiao, You-Lin; Dawsey, Sanford M et al. (2003) Prospective study of serum retinol, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China. Cancer Causes Control 14:645-55
Taylor, Philip R; Qiao, You-Lin; Abnet, Christian C et al. (2003) Prospective study of serum vitamin E levels and esophageal and gastric cancers. J Natl Cancer Inst 95:1414-6