Trial Information

Nutritional Intervention Trials in Linxian China- Continued Follow-up

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.