Nutrition Intervention Trials in Linxian Follow-up Study

NCT ID: NCT00342654

Last Updated: 2026-01-26

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 32902 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 1999-05-20
• Study Completion Date: 2025-12-02

Brief Summary

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.

Detailed 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 approximately 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 approximately 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 approximately 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 (approximately 2500) and controls (approximately 2500) previously identified from 1991-1996, as well as using new cancer and stroke cases and controls for the period 1996-2004 (approximately 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.

Conditions

Esophageal Cancer; Gastric Cancer

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: OTHER

Study Groups

1

Participants from two large, nutritional intervention trials that were conducted in Linxian, China between 1985-1991.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• No eligibility criteria listed.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Cancer Institute (NCI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Christian C Abnet, Ph.D.

Role: PRINCIPAL_INVESTIGATOR

National Cancer Institute (NCI)

Locations

Cancer Institute and Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Countries

China

References

Murphy G, Freedman ND, Michel A, Fan JH, Taylor PR, Pawlita M, Qiao YL, Zhang H, Yu K, Abnet CC, Dawsey SM. Prospective study of Helicobacter pylori antigens and gastric noncardia cancer risk in the nutrition intervention trial cohort. Int J Cancer. 2015 Oct 15;137(8):1938-46. doi: 10.1002/ijc.29543. Epub 2015 May 5.

Reference Type: BACKGROUND

PMID: 25845708 (View on PubMed)

Abnet CC, Freedman ND, Hu N, Wang Z, Yu K, Shu XO, Yuan JM, Zheng W, Dawsey SM, Dong LM, Lee MP, Ding T, Qiao YL, Gao YT, Koh WP, Xiang YB, Tang ZZ, Fan JH, Wang C, Wheeler W, Gail MH, Yeager M, Yuenger J, Hutchinson A, Jacobs KB, Giffen CA, Burdett L, Fraumeni JF Jr, Tucker MA, Chow WH, Goldstein AM, Chanock SJ, Taylor PR. A shared susceptibility locus in PLCE1 at 10q23 for gastric adenocarcinoma and esophageal squamous cell carcinoma. Nat Genet. 2010 Sep;42(9):764-7. doi: 10.1038/ng.649. Epub 2010 Aug 22.

Reference Type: BACKGROUND

PMID: 20729852 (View on PubMed)

Qiao YL, Dawsey SM, Kamangar F, Fan JH, Abnet CC, Sun XD, Johnson LL, Gail MH, Dong ZW, Yu B, Mark SD, Taylor PR. Total and cancer mortality after supplementation with vitamins and minerals: follow-up of the Linxian General Population Nutrition Intervention Trial. J Natl Cancer Inst. 2009 Apr 1;101(7):507-18. doi: 10.1093/jnci/djp037. Epub 2009 Mar 24.

Reference Type: BACKGROUND

PMID: 19318634 (View on PubMed)

Yang H, Wang J, Wang X, Sun W, Tong C, Fan J, Qiao Y, Abnet CC. Weight change and all-cause and cause-specific mortality: A 25-year follow-up study. Chin Med J (Engl). 2024 May 20;137(10):1169-1178. doi: 10.1097/CM9.0000000000002970. Epub 2024 Jan 29.

Reference Type: DERIVED

PMID: 38282387 (View on PubMed)

Yang H, Wang JB, Wang XK, Fan JH, Qiao YL. Association between type of drinking water and upper gastrointestinal cancer incidence in the Linxian General Population. BMC Cancer. 2023 May 4;23(1):397. doi: 10.1186/s12885-023-10887-2.

Reference Type: DERIVED

PMID: 37142988 (View on PubMed)

Fan JH, Wang JB, Wang SM, Abnet CC, Qiao YL, Taylor PR. Longitudinal change in blood pressure is associated with cardiovascular disease mortality in a Chinese cohort. Heart. 2018 Nov;104(21):1764-1771. doi: 10.1136/heartjnl-2017-312850. Epub 2018 Apr 24.

Reference Type: DERIVED

PMID: 29691288 (View on PubMed)

Wang SM, Taylor PR, Fan JH, Pfeiffer RM, Gail MH, Liang H, Murphy GA, Dawsey SM, Qiao YL, Abnet CC. Effects of Nutrition Intervention on Total and Cancer Mortality: 25-Year Post-trial Follow-up of the 5.25-Year Linxian Nutrition Intervention Trial. J Natl Cancer Inst. 2018 Nov 1;110(11):1229-1238. doi: 10.1093/jnci/djy043.

Reference Type: DERIVED

PMID: 29617851 (View on PubMed)

Fan JH, Wang JB, Wang SM, Abnet CC, Qiao YL, Taylor PR. Body mass index and risk of gastric cancer: A 30-year follow-up study in the Linxian general population trial cohort. Cancer Sci. 2017 Aug;108(8):1667-1672. doi: 10.1111/cas.13292. Epub 2017 Jun 30.

Reference Type: DERIVED

PMID: 28594442 (View on PubMed)

Chen W, Wang JB, Abnet CC, Dawsey SM, Fan JH, Yin LY, Yin J, Taylor PR, Qiao YL, Freedman ND. Association between C-reactive protein, incident liver cancer, and chronic liver disease mortality in the Linxian Nutrition Intervention Trials: a nested case-control study. Cancer Epidemiol Biomarkers Prev. 2015 Feb;24(2):386-92. doi: 10.1158/1055-9965.EPI-14-1038. Epub 2015 Jan 22.

Reference Type: DERIVED

PMID: 25613115 (View on PubMed)

Wang JB, Abnet CC, Fan JH, Qiao YL, Taylor PR. The randomized Linxian Dysplasia Nutrition Intervention Trial after 26 years of follow-up: no effect of multivitamin supplementation on mortality. JAMA Intern Med. 2013 Jul 8;173(13):1259-61. doi: 10.1001/jamainternmed.2013.6066. No abstract available.

Reference Type: DERIVED

PMID: 23712839 (View on PubMed)

Other Identifiers

OH99-C-N031

Identifier Type: -

Identifier Source: secondary_id

999999031

Identifier Type: -

Identifier Source: org_study_id