Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population.
BACKGROUND
Gastric cancer is one of the most common malignancies worldwide. Histopathologic studies have identified a sequence of changes in the gastric mucosa that mark the slow progression from normal tissue to carcinoma. Epidemiologic evidence suggests that a diet rich in fresh fruit and vegetables could be a protective factor against this disease. This effect may be mediated through antioxidant vitamins.


METHODS
A randomized, double-blind chemoprevention trial was conducted among 1980 subjects in Tachira State, Venezuela (whose population is at high risk for gastric cancer), to determine the effect of dietary supplementation with vitamin C, vitamin E, and beta-carotene on the progression and regression of precancerous gastric lesions. Subjects were randomly assigned to receive either a combination of vitamin C (750 mg/day), vitamin E (600 mg/day), and beta-carotene (18 mg/day) or placebo for 3 years. Changes in the gastric mucosa were determined by histologic diagnosis based on five biopsies taken from prespecified areas of the stomach at baseline and annually for 3 years. All biopsies were reviewed by a single expert pathologist. Progression rates (and regression rates) were calculated by comparing the first and last available gastroscopies for each subject and dividing the number of subjects whose diagnoses increased (decreased) in severity by the total follow-up time. Overall rate ratios were calculated by Poisson regression, controlling for baseline diagnosis. All statistical tests were two-sided.


RESULTS
Median plasma vitamin levels were increased in the treatment group between baseline and 1 year after randomization from 0.43 micromol/L (interquartile range [IQR] = 0.26-0.69) to 2.89 micromol/L (IQR = 1.76-4.22) for beta-carotene, from 26.7 micromol/L (IQR = 23.1-31.2) to 54.9 micromol/L (IQR = 42.8-67.6) for alpha-tocopherol, and from 47.70 micromol/L (IQR = 36.9-58.5) to 61.9 micromol/L (IQR = 52.2-72.7) for vitamin C. Overall progression rates per 100 person-years were 74.3 in the placebo group and 67.8 in the group randomly assigned to vitamins. Overall regression rates were 109.4 in the placebo group and 116.5 in the group randomly assigned to vitamins. There was no statistically significant difference in progression rate (rate ratio = 0.92, 95% confidence interval [CI] = 0.74 to 1.15) or regression rate (rate ratio = 1.09, 95% CI = 0.90 to 1.33) between vitamin and placebo groups.


CONCLUSIONS
Supplementation with antioxidant micronutrients is not an effective tool for gastric cancer control in this high-risk population. The results of this trial are consistent with previous findings on the lack of effect of nutritional supplementation on precancerous gastric lesions.
Plummer
Martyn
M
International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon cedex 08, France. plummer@iarc.fr
Vivas
Jorge
J
Lopez
Gladys
G
Bravo
Juan Carlos
JC
Peraza
Simon
S
Carillo
Elsa
E
Cano
Elsa
E
Castro
Denis
D
Andrade
Olga
O
Sánchez
Victor
V
Garcia
Rita
R
Buiatti
Eva
E
Aebischer
Claude
C
Franceschi
Silvia
S
Oliver
Walter
W
Muñoz
Nubia
N
D000328:Adult; D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage* / Q000378:metabolism; D001205:Ascorbic Acid / Q000008:administration & dosage; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000473:pathology; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects* / Q000473:pathology*; D005773:Gastroscopy; D016481:Helicobacter Infections / Q000150:complications; D016480:Helicobacter pylori; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D011230:Precancerous Conditions / Q000097:blood / Q000175:diagnosis / Q000382:microbiology / Q000517:prevention & control*; D018570:Risk Assessment; D018401:Sample Size; D012907:Smoking / Q000009:adverse effects; D013274:Stomach Neoplasms / Q000097:blood / Q000175:diagnosis / Q000382:microbiology / Q000517:prevention & control*; D017211:Treatment Failure; D014687:Venezuela; D014810:Vitamin E / Q000008:administration & dosage; D014815:Vitamins / Q000008:administration & dosage* / Q000097:blood; D019207:beta Carotene / Q000008:administration & dosage
D000975:Antioxidants; D014815:Vitamins; D019207:beta Carotene; D014810:Vitamin E; D001205:Ascorbic Acid