NCT00342654

Nutrition Intervention Trials in Linxian Follow-up Study

Completed Last updated 8 April 2026

What this trial tests

trial in Esophageal Cancer in 32,902 participants. Completed in 2 December 2025.

Timeline

20 May 1999

Primary endpoint
2 December 2025

2 December 2025

Quick facts

Lead sponsor	National Cancer Institute (NCI)
Status	Completed
Study type	OBSERVATIONAL
Enrollment	32,902
Start date	20 May 1999
Primary completion	2 December 2025
Estimated completion	2 December 2025
Sites	1 location across China

Conditions studied

• Esophageal Cancer — all drugs for Esophageal Cancer →
• Gastric Cancer — all drugs for Gastric Cancer →

Sponsor

National Cancer Institute (NCI)

Who can join

Adults 18 to 100, any sex, with Esophageal Cancer or Gastric Cancer. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

Two large, nutritional intervention trials were conducted in Linxian, China between 1985-1991. These trials tested the effect of multiple vitamins and minerals in the prevention of esophageal cancer in a population with the highest known rate for this disease in the world. Results from the trials showed that Beta-carotene + Vitamin E + selenium reduced total mortality, total cancer mortality, and stomach cancer incidence and mortality. Multivitamins/minerals also showed reduction in premalignant lesions. Preliminary follow-up data obtained for the time period after cessation of intervention in 1991 suggests that the observed benefit for total and cancer mortality is reduced but that the benefit for stomach cancer remains.

The objectives of the follow-up study are: (1) to continue to determine cancer incidence and all causes of mortality in trial participants after intervention to permit examination of potential effects of the interventions on total and cause-specific mortality and cancer incidence in the post-intervention period; (2) to conduct a cross-sectional nutritional survey in a subsample of living trial participants to evaluate their nutritional status, asses the validity of dietary questionnaires, and relate neurologic status to vitamin B12 plasma levels; (3) to collect a blood sample from all living trial participants to permit further etiologic investigations of genetic and environmental hypotheses; and (4) to perform nested case-control studies of selected genetic and environmental hypotheses.

To accomplish the objectives of the follow-up study, we will: (1) determine updated vital status and cancer status data on all trial participants via monthly checks of village doctor records and quarterly checks of the Linxian Cancer Registry; conduct a Vital/Cancer Status Interview Survey among all (n-34,000 trial participants (or their surrogates); identify, collect, and store all available diagnostic materials for trial participants identified as having developed cancer or died with cancer during the follow-up period; (2) conduct a Nutritional Survey on a subsample (n-1000) of living trial participants that will include (a) a physical exam and brief medical history, (b) a neurologic history, (c) a cognitive function exam, (d) a hair/mouth skin exam, (e) a neurological exam, (f) a nutritional questionnaire, and (g) collection of a blood sample for hematologic/biochemical analyses; (3) conduct a Blood Collection Survey of all living trial participants (n-23,000) to obtain (a) a physical exam and brief medical history and (b) a single 10-ml blood sample for separation and preservation as WBCs (both viable and nonviable), RBCs, and plasma for genetic (e.g., xenobiotic polymorphisms) and environmental (e.g., plasma ascorbic acid) hypothesis testing; and (4) perform Nested Case-Control Studies of selected genetic and environmental hypothesis related to the etiology and prevention of esophageal cancer and stroke. These will be done using serum from the new cancer and stroke cases (-2500) and controls (-2500) previously identified from 1991-1996, as well as using new cancer and stroke cases and controls for the period 1996-2004 (-9000).

The followup for endpoints will continue monthly for an additional 5 years (through the year 2003). The Nutritional Survey and Blood Collection Survey will be conducted in the spring of 1999. The Nested Case-Control studies will be performed annually beginning in 2000, and the Vital/Cancer Interview Survey will be conducted in the Spring of 2001....

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial.
   Qiao YL, Dawsey SM, Kamangar F, Fan JH, et al · · 2009 · cited 215× · PMID 19318634 · DOI 10.1093/jnci/djp037
2. Effects of Nutrition Intervention on Total and Cancer Mortality: 25-Year Post-trial Follow-up of the 5.25-Year Linxian Nutrition Intervention Trial.
   Wang SM, Taylor PR, Fan JH, Pfeiffer RM, et al · · 2018 · cited 44× · PMID 29617851 · DOI 10.1093/jnci/djy043
3. Association between C-reactive protein, incident liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case-control study.
   Chen W, Wang JB, Abnet CC, Dawsey SM, et al · · 2015 · cited 32× · PMID 25613115 · DOI 10.1158/1055-9965.epi-14-1038
4. Molecular mechanisms underlying the action of carcinogens in gastric cancer with a glimpse into targeted therapy.
   Patrad E, Khalighfard S, Amiriani T, Khori V, et al · · 2022 · cited 23× · PMID 36149600 · DOI 10.1007/s13402-022-00715-3
5. The randomized Linxian Dysplasia Nutrition Intervention Trial after 26 years of follow-up: no effect of multivitamin supplementation on mortality.
   Wang JB, Abnet CC, Fan JH, Qiao YL, et al · · 2013 · cited 23× · PMID 23712839 · DOI 10.1001/jamainternmed.2013.6066
6. Drugs for preventing lung cancer in healthy people.
   Cortés-Jofré M, Rueda JR, Asenjo-Lobos C, Madrid E, et al · · 2020 · cited 22× · PMID 32130738 · DOI 10.1002/14651858.cd002141.pub3
7. Longitudinal change in blood pressure is associated with cardiovascular disease mortality in a Chinese cohort.
   Fan JH, Wang JB, Wang SM, Abnet CC, et al · · 2018 · cited 21× · PMID 29691288 · DOI 10.1136/heartjnl-2017-312850
8. Body mass index and risk of gastric cancer: A 30-year follow-up study in the Linxian general population trial cohort.
   Fan JH, Wang JB, Wang SM, Abnet CC, et al · · 2017 · cited 19× · PMID 28594442 · DOI 10.1111/cas.13292