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Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population.

Abstract

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.

CONCLUSION

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.

Links

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  • Authors+Show Affiliations

    ,

    International Agency for Research on Cancer, 150 cours Albert Thomas, 69372 Lyon cedex 08, France. plummer@iarc.fr

    , , , , , , , , , , , , , ,

    Source

    Journal of the National Cancer Institute 99:2 2007 Jan 17 pg 137-46

    MeSH

    Adult
    Aged
    Antioxidants
    Ascorbic Acid
    Cell Transformation, Neoplastic
    Disease Progression
    Double-Blind Method
    Female
    Gastric Mucosa
    Gastroscopy
    Helicobacter Infections
    Helicobacter pylori
    Humans
    Logistic Models
    Male
    Middle Aged
    Patient Selection
    Precancerous Conditions
    Risk Assessment
    Sample Size
    Smoking
    Stomach Neoplasms
    Treatment Failure
    Venezuela
    Vitamin E
    Vitamins
    beta Carotene

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    17227997

    Citation

    Plummer, Martyn, et al. "Chemoprevention of Precancerous Gastric Lesions With Antioxidant Vitamin Supplementation: a Randomized Trial in a High-risk Population." Journal of the National Cancer Institute, vol. 99, no. 2, 2007, pp. 137-46.
    Plummer M, Vivas J, Lopez G, et al. Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. J Natl Cancer Inst. 2007;99(2):137-46.
    Plummer, M., Vivas, J., Lopez, G., Bravo, J. C., Peraza, S., Carillo, E., ... Muñoz, N. (2007). Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. Journal of the National Cancer Institute, 99(2), pp. 137-46.
    Plummer M, et al. Chemoprevention of Precancerous Gastric Lesions With Antioxidant Vitamin Supplementation: a Randomized Trial in a High-risk Population. J Natl Cancer Inst. 2007 Jan 17;99(2):137-46. PubMed PMID: 17227997.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Chemoprevention of precancerous gastric lesions with antioxidant vitamin supplementation: a randomized trial in a high-risk population. AU - Plummer,Martyn, AU - Vivas,Jorge, AU - Lopez,Gladys, AU - Bravo,Juan Carlos, AU - Peraza,Simon, AU - Carillo,Elsa, AU - Cano,Elsa, AU - Castro,Denis, AU - Andrade,Olga, AU - Sánchez,Victor, AU - Garcia,Rita, AU - Buiatti,Eva, AU - Aebischer,Claude, AU - Franceschi,Silvia, AU - Oliver,Walter, AU - Muñoz,Nubia, PY - 2007/1/18/pubmed PY - 2007/2/10/medline PY - 2007/1/18/entrez SP - 137 EP - 46 JF - Journal of the National Cancer Institute JO - J. Natl. Cancer Inst. VL - 99 IS - 2 N2 - 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. CONCLUSION: 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. SN - 1460-2105 UR - https://www.unboundmedicine.com/medline/citation/17227997/Chemoprevention_of_precancerous_gastric_lesions_with_antioxidant_vitamin_supplementation:_a_randomized_trial_in_a_high_risk_population_ L2 - https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djk017 DB - PRIME DP - Unbound Medicine ER -