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Statins, Antioxidants and Green Tea
Statins, the widely prescribed class of HMG CoA–inhibiting cholesterol-lowering drugs, have been found in numerous epidemiologic studies to be associated with decreased risks of various malignancies. In addition to their cholesterol-lowering properties, statins also have antiproliferative and proapoptotic effects.276 A population-based case-control study from Taiwan found a significantly reduced risk of gastric cancer in patients prescribed statins (odds ratio, 0.68), with greater risk reduction observed among those with the highest cumulative statin use.277 In a separate case-control study of diabetics from South Korea, a history of statin use was associated with an 80% reduced likelihood of gastric cancer.278 A pharmacy database study from the Netherlands found a significant association between statin use and a decreased risk of cancer of any type; however, there was no significant association with gastric cancer, although the number of cases was relatively small.279 Future randomized controlled trials of various statins in patients at high risk for gastric cancer will help define the role of this class of drugs as chemopreventive agents.
Chronic inflammatory states such as Hp gastritis can result in the generation of free radicals derived from oxygen and nitrogen.280 These free radicals can promote carcinogenesis via numerous different means, including direct DNA damage and inhibition of DNA repair mechanisms, inhibition of apoptosis, and activation of cellular proliferation pathways. Antioxidants such as carotenoids and vitamins C and E bind with reactive oxygen and nitrogen species to neutralize their damaging effects.
Epidemiologic data support a relationship between increased antioxidant intake and reduced risk of gastric cancer.281-285 In a nested case-control study from Japan, low plasma beta carotene levels were associated with an increased risk of gastric cancer.283 A case-control study from Korea found that elevated nitrate/antioxidant intake ratios were associated with increased risk of gastric cancer.284In a Swedish cohort study, high levels of vitamin A, retinol, and alpha and beta carotene intake were associated with a 50% risk reduction in gastric cancer.285
Randomized controlled trials have shown inconsistent effects of antioxidant supplementation on gastric cancer risk. In a randomized placebo-controlled trial of antioxidants (either vitamin A, C, or E) in patients with precancerous gastric lesions (nonatrophic or atrophic gastritis, intestinal metaplasia, or dysplasia), antioxidant supplementation did not result in either reduced histologic progression or increased histologic regression.286 A randomized controlled trial in China also found no effect of combined vitamin C, E, and selenium supplementation on the prevalence of a combined end point of atrophic gastritis, intestinal metaplasia, dysplasia, or cancer.287 In a 10-year follow-up of the General Population Nutrition Intervention Trial in China, subjects who received a combination of selenium, vitamin E, and beta carotene were found to have reduced mortality from gastric cancer.288 Given a lack of convincing chemopreventive effect as well as the results of the Beta Carotene and Retinol Efficacy Trial, in which subjects who received beta carotene and vitamin A had an increased risk of lung cancer,289 antioxidant supplementation for the prevention of gastric cancer cannot yet be recommended.
Green tea is widely consumed in Asian countries and is hypothesized to have protective effects against cancer of the upper digestive tract. Polyphenols and other metabolites present in green teas, such as epigallocatechin-3-gallate (EGCG) and other catechins, have a variety of antitumor effects, including induction of apoptosis, inhibition of tumor cell growth and proliferation, and reduction in COX-2 expression.290-292 EGCG also has antioxidant properties and may have anti-inflammatory properties as well.293,294 While case-control studies have shown an inverse association between the risk of gastric cancer and the consumption of green tea, cohort studies have largely failed to show an association.295,296 One cohort study from Japan did report a reduced risk of gastric cancer in women with high green tea consumption, but no change in risk among men.297 Thus, in the absence of prospective controlled trials, green tea cannot be recommended as chemoprevention for gastric cancer.