Bjelakovic Goran, Nikolova Dimitrinka, Simonetti Rosa G, Gluud Christian
The Cochrane Hepato-Biliary Group, Copenhagen Trial Unit, Centre for Clinical Intervention Research, Copenhagen University Hospital, H:S Rigshospitalet, Copenhagen, Denmark.
Lancet. 2004;364(9441):1219-28. doi: 10.1016/S0140-6736(04)17138-9.
Oxidative stress can cause cancer. Our aim was to establish whether antioxidant supplements reduce the incidence of gastrointestinal cancer and mortality.
With the Cochrane Collaboration methodology, we reviewed all randomised trials comparing antioxidant supplements with placebo for prevention of gastrointestinal cancers. We searched electronic databases and reference lists (February, 2003). Outcome measures were incidence of gastrointestinal cancers, overall mortality, and adverse effects. Outcomes were analysed with fixed-effect and random-effects model meta-analyses and were reported as relative risk with 95% CIs.
We identified 14 randomised trials (n=170,525). Trial quality was generally high. Heterogeneity of results was low to moderate. Neither the fixed-effect (relative risk 0.96, 95% CI 0.88-1.04) nor random-effects meta-analyses (0.90, 0.77-1.05) showed significant effects of supplementation with beta-carotene, vitamins A, C, E, and selenium (alone or in combination) versus placebo on oesophageal, gastric, colorectal, pancreatic, and liver cancer incidences. In seven high-quality trials (n=131727), the fixed-effect model showed that antioxidant significantly increased mortality (1.06, 1.02-1.10), unlike the random-effects meta-analysis (1.06, 0.98-1.15). Low-quality trials showed no significant effect of antioxidant supplementation on mortality. The difference between the mortality estimates in high-quality and low-quality trials was significant (Z=2.10, p=0.04 by test of interaction). beta-carotene and vitamin A (1.29, 1.14-1.45) and beta-carotene and vitamin E (1.10, 1.01-1.20) significantly increased mortality, whereas beta-carotene alone only tended to increase mortality (1.05, 0.99-1.11). In four trials (three with unclear or inadequate methodology), selenium showed significant beneficial effect on the incidence of gastrointestinal cancer.
We could not find evidence that antioxidant supplements can prevent gastrointestinal cancers; on the contrary, they seem to increase overall mortality. The potential preventive effect of selenium should be studied in adequate randomised trials.
氧化应激可引发癌症。我们的目的是确定抗氧化剂补充剂是否能降低胃肠道癌症的发病率和死亡率。
采用Cochrane协作网的方法，我们检索了所有比较抗氧化剂补充剂与安慰剂预防胃肠道癌症的随机试验。我们检索了电子数据库和参考文献列表（2003年2月）。观察指标为胃肠道癌症的发病率、总死亡率和不良反应。采用固定效应和随机效应模型进行荟萃分析，并将结果报告为相对风险及95%可信区间。
我们确定了14项随机试验（n = 170525）。试验质量总体较高。结果的异质性为低到中度。固定效应荟萃分析（相对风险0.96，95%可信区间0.88 - 1.04）和随机效应荟萃分析（0.90，0.77 - 1.05）均未显示补充β-胡萝卜素、维生素A、C、E和硒（单独或联合使用）与安慰剂相比对食管癌、胃癌、结直肠癌、胰腺癌和肝癌的发病率有显著影响。在7项高质量试验（n = 131727）中，固定效应模型显示抗氧化剂显著增加死亡率（1.06，1.02 - 1.10），而随机效应荟萃分析结果则不同（1.06，0.98 - 1.15）。低质量试验显示抗氧化剂补充对死亡率无显著影响。高质量和低质量试验中死亡率估计值的差异具有显著性（Z = 2.10，交互作用检验p = 0.04）。β-胡萝卜素与维生素A（1.29，1.14 - 1.45）以及β-胡萝卜素与维生素E（1.10，1.01 - 1.20）显著增加死亡率，而单独使用β-胡萝卜素仅倾向于增加死亡率（1.05，0.99 - 1.11）。在4项试验（3项方法不明确或不充分）中，硒对胃肠道癌症的发病率显示出显著的有益作用。
我们未找到证据表明抗氧化剂补充剂可预防胃肠道癌症；相反，它们似乎会增加总死亡率。硒的潜在预防作用应在充分的随机试验中进行研究。
