Cortés-Jofré Marcela, Rueda José-Ramón, Asenjo-Lobos Claudia, Madrid Eva, Bonfill Cosp Xavier
Universidad Católica de la Santísima, Concepción, Chile.
Autonomous University of Barcelona, Doctoral Program in Research Methodology and Public Health, Barcelona, Spain.
Cochrane Database Syst Rev. 2020 Mar 4;3(3):CD002141. doi: 10.1002/14651858.CD002141.pub3.
This is the second update of this Cochrane Review. Some studies have suggested a protective effect of antioxidant nutrients and higher dietary levels of fruits and vegetables on lung cancer.
To determine whether vitamins and minerals and other potential agents, alone or in combination, reduce lung cancer incidence and lung cancer mortality in healthy populations.
We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews.
We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer.
Four review authors independently selected the trials to be included in the review, assessed their methodological quality and extracted data. For dichotomous outcomes we calculated risk ratios (RRs) and 95% confidence intervals (CIs) and pooled results using the random-effects model. We assessed the risk of bias using Cochrane's 'Risk of bias' assessment tool and certainty of evidence using the GRADE approach.
In this update, we identified three new trials for a total of 12 studies. Six analysed vitamin A, three vitamin C, three combined vitamin D3 + calcium, four vitamin E combined with other products, one selenium supplements and nine studied combinations of two or more products. Four studies included only men and five only women. Vitamin A results in little to no difference in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19; 5 RCTs, 212314 participants; high-certainty evidence) and lung cancer mortality (RR 1.06, 95% CI 0.81 to 1.38; 3 RCTs, 190118 participants; high-certainty evidence). But in smokers or asbestos workers vitamin A increases the risk of lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 RCTs, 43995 participants; high-certainty evidence), lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38; 2 RCTs, 29426 participants; high-certainty evidence) and all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 RCTs, 32883 participants; high-certainty evidence). Vitamin A increases the risk of minor side effects, such as yellowing of the skin and minor gastrointestinal symptoms (high-certainty evidence). Vitamin C likely results in little to no difference in lung cancer incidence (RR 1.29, 95% CI 0.67 to 2.49; 2 RCTs, 14953 participants; moderate-certainty evidence). In women, vitamin C increases the risk of lung cancer incidence (RR 1.84, 95% CI 1.14 to 2.95; 1 RCT, 7627 participants; high-certainty evidence). In men, vitamin C results in little to no difference in mortality for lung cancer (RR 0.81, 95% CI 0.53 to 1.23; 1 RCT, 7326 participants; high-certainty evidence). Vitamin D + calcium may result in little to no difference in lung cancer incidence in postmenopausal women (RR 0.90, 95% CI 0.39 to 2.08; 3 RCTs, 37601 women; low-certainty evidence). Vitamin E results in little to no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 RCTs, 36841 participants; high-certainty evidence) or to lung cancer mortality (RR 0.96, 95% CI 0.77 to 1.18; 2 RCTs, 29214 participants; high-certainty evidence), but increases the risk of haemorrhagic strokes (hazard ratio (HR), 1.74, 95% CI 1.04 to 2.91; 1 RCT, 14641 participants; high-certainty evidence). Calcium results in little to no difference in lung cancer incidence in postmenopausal women (RR 0.65, 95% CI 0.13 to 3.18; 1 RCT, 733 participants) or in risk of renal calculi (RR 1.94, 95% CI 0.20 to 18.57; 1 RCT, 733 participants; low-certainty evidence). Selenium in men results in little to no difference in lung cancer incidence (RR 1.11, 95% CI 0.80 to 1.54; 1 RCT, 17448 participants; high-certainty evidence) and lung cancer mortality (RR 1.09, 95% CI 0.72 to 1.66; 1 RCT, 17448 participants; high-certainty evidence) and increases the risk for grade 1 to 2 dermatitis (RR 1.16, 95% CI 1.04 to 1.31; 1 RCT, 17448 participants; high-certainty evidence) and for alopecia (RR 1.28, 95% CI 1.07 to 1.53; 1 RCT, 17448 participants; high-certainty evidence). The combination of vitamins A, C, E + selenium + zinc results in little to no difference in lung cancer incidence (RR 0.64, 95% CI 0.28 to 1.48; 1 RCT, 12741 participants; high-certainty evidence).
AUTHORS' CONCLUSIONS: Well-designed RCTs have shown no beneficial effect of supplements for the prevention of lung cancer and lung cancer mortality in healthy people. Vitamin A supplements increase lung cancer incidence and mortality in smokers or persons exposed to asbestos. Vitamin C increases lung cancer incidence in women. Vitamin E increases the risk of haemorrhagic strokes.
这是本Cochrane系统评价的第二次更新。一些研究表明抗氧化营养素以及较高的水果和蔬菜膳食摄入量对肺癌具有保护作用。
确定维生素、矿物质及其他潜在药物单独或联合使用是否能降低健康人群的肺癌发病率和肺癌死亡率。
我们检索了1974年至2019年5月期间的Cochrane系统评价数据库、MEDLINE和Embase，并筛选了已发表研究和综述中包含的参考文献。
我们纳入了比较维生素或矿物质补充剂与安慰剂的随机对照试验（RCT），这些试验针对健康人群，旨在预防肺癌。
四位综述作者独立选择纳入综述的试验，评估其方法学质量并提取数据。对于二分法结局，我们计算风险比（RR）和95%置信区间（CI），并使用随机效应模型汇总结果。我们使用Cochrane的“偏倚风险”评估工具评估偏倚风险，并使用GRADE方法评估证据的确定性。
在本次更新中，我们共识别出三项新试验，总计12项研究。六项研究分析了维生素A，三项分析了维生素C，三项分析了维生素D3加钙的组合，四项分析了维生素E与其他产品的组合，一项分析了硒补充剂，九项研究了两种或更多产品的组合。四项研究仅纳入男性，五项仅纳入女性。维生素A对肺癌发病率（RR 1.09，95% CI 1.00至1.19；5项RCT，212314名参与者；高确定性证据）和肺癌死亡率（RR 1.06，95% CI 0.81至1.38；3项RCT，190118名参与者；高确定性证据）几乎没有差异。但在吸烟者或石棉工人中，维生素A会增加肺癌发病率（RR 1.10，95% CI 1.01至1.20；3项RCT，43995名参与者；高确定性证据）、肺癌死亡率（RR 1.18，95% CI 1.01至1.38；2项RCT，29426名参与者；高确定性证据）以及全因死亡率（RR 1.09，95% CI 1.05至1.13；2项RCT，32883名参与者；高确定性证据）。维生素A会增加轻微副作用的风险，如皮肤变黄和轻微胃肠道症状（高确定性证据）。维生素C对肺癌发病率可能几乎没有差异（RR 1.29，95% CI 0.67至2.49；2项RCT，14953名参与者；中等确定性证据）。在女性中，维生素C会增加肺癌发病率（RR 1.84，95% CI 1.14至2.95；1项RCT，7627名参与者；高确定性证据）。在男性中，维生素C对肺癌死亡率几乎没有差异（RR 0.81，95% CI 0.53至1.23；1项RCT，7326名参与者；高确定性证据）。维生素D加钙对绝经后女性的肺癌发病率可能几乎没有差异（RR 0.90，95% CI 0.39至2.08；3项RCT，37601名女性；低确定性证据）。维生素E对肺癌发病率（RR 1.01，95% CI 0.90至1.14；3项RCT，36841名参与者；高确定性证据）或肺癌死亡率（RR 0.96，95% CI 0.77至1.18；2项RCT，29214名参与者；高确定性证据）几乎没有差异，但会增加出血性中风的风险（风险比（HR），1.74，95% CI 1.04至2.91；1项RCT，14641名参与者；高确定性证据）。钙对绝经后女性的肺癌发病率（RR 0.65，95% CI 0.13至3.18；1项RCT，733名参与者）或肾结石风险（RR 1.94，95% CI 0.20至18.57；1项RCT，733名参与者；低确定性证据）几乎没有差异。男性补充硒对肺癌发病率（RR 1.11，95% CI 0.80至1.54；1项RCT，17448名参与者；高确定性证据）和肺癌死亡率（RR 1.09，95% CI 0.72至1.66；1项RCT，17448名参与者；高确定性证据）几乎没有差异，但会增加1至2级皮炎的风险（RR 1.16，95% CI 1.04至1.31；1项RCT，17448名参与者；高确定性证据）和脱发的风险（RR 1.28，95% CI 1.07至1.53；1项RCT，17448名参与者；高确定性证据）。维生素A、C、E加硒加锌的组合对肺癌发病率几乎没有差异（RR 0.64，95% CI 0.28至1.48；1项RCT，12741名参与者；高确定性证据）。
设计良好的随机对照试验表明，补充剂对预防健康人群的肺癌和肺癌死亡率没有益处。维生素A补充剂会增加吸烟者或接触石棉者的肺癌发病率和死亡率。维生素C会增加女性的肺癌发病率。维生素E会增加出血性中风的风险。
