Drugs for preventing lung cancer in healthy people

Our plain-English summary of Drugs for preventing lung cancer in healthy people, by M. Cortés-Jofré, J.R. Rueda, C. Asenjo-Lobos, et al (The Cochrane Database of Systematic Reviews, 2020).

The study

• Authors: M. Cortés-Jofré, J.R. Rueda, C. Asenjo-Lobos, E. Madrid, X. Bonfill Cosp
• Journal: The Cochrane Database of Systematic Reviews
• Published: 2020;3(3):CD002141
• Type of article: Meta-analysis, Systematic review
• Cited by: 26 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: 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.

Objectives: 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.

Search Methods: We searched CENTRAL, MEDLINE and Embase from 1974 to May 2019 and screened references included in published studies and reviews.

Selection Criteria: We included randomised controlled trials (RCTs) comparing vitamins or mineral supplements with placebo, administered to healthy people with the aim of preventing lung cancer.

Data Collection And Analysis: 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.

Main Results: 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.

Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.

In plain English

This Cochrane systematic review pooled randomised controlled trials that compared vitamin or mineral supplements with placebo for preventing lung cancer in healthy people. Searching to May 2019, the authors included 12 trials. Two of them enrolled only smokers or people exposed to asbestos. Across five trials (212314 participants), vitamin A (beta-carotene or retinol) showed a small increase in lung cancer incidence (RR 1.09, 95% CI 1.00 to 1.19). In the high-risk group (smokers and asbestos workers), vitamin A was linked to higher lung cancer incidence (RR 1.10, 95% CI 1.01 to 1.20; 3 trials, 43995 participants) and higher all-cause mortality (RR 1.09, 95% CI 1.05 to 1.13; 2 trials, 32883 participants). Among smokers in two trials (29426 participants), vitamin A was also linked to higher lung cancer mortality (RR 1.18, 95% CI 1.01 to 1.38). In one trial of 7627 women, vitamin C was linked to more lung cancer (RR 1.84, 95% CI 1.14 to 2.95). In one trial, vitamin E was linked to more haemorrhagic strokes (HR 1.74, 95% CI 1.04 to 2.91). The authors concluded there was no evidence that the supplements prevented lung cancer. They also concluded that vitamin A increased lung cancer and deaths in smokers and people exposed to asbestos.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cochrane systematic review and meta-analysis of randomised controlled trials (second update of the review)
• Who was studied: 12 trials of healthy adults aged 35 to 84 at the start of treatment. Eight trials were in the USA, one in the USA, Canada and Puerto Rico, one in China and two in Europe. Four trials included only men and five only women. Two trials (ATBC 1994 and CARET/Omenn 1996) enrolled only high-risk people. CARET included 4060 male workers exposed to asbestos and 14,254 heavy smokers. Databases were searched from 1974 to May 2019.
• Exposure: Oral supplements compared with placebo: vitamin A (beta-carotene or retinol), vitamin C, vitamin D plus calcium, vitamin E (alpha-tocopherol), calcium, selenium, and combinations. Smoking and asbestos exposure were used to define a high-risk subgroup.
• Main results:
  • Vitamin A versus placebo, all participants (5 trials, 212314 participants): small increase in lung cancer incidence, RR 1.09 (95% CI 1.00 to 1.19).
  • Vitamin A, high-risk people (smokers and those exposed to asbestos; 3 trials, 43995 participants): higher lung cancer incidence, RR 1.10 (95% CI 1.01 to 1.20).
  • Vitamin A, low-risk people (3 trials, 168319 participants): no difference in lung cancer incidence, RR 0.99 (95% CI 0.69 to 1.42).
  • Vitamin A, lung cancer mortality among smokers in two trials (ATBC 1994 and the smoker subgroup of Hennekens 1996; 29426 participants): RR 1.18 (95% CI 1.01 to 1.38).
  • Vitamin A, all-cause mortality in two trials of high-risk participants only (ATBC 1994 and Omenn 1996; 32883 participants): RR 1.09 (95% CI 1.05 to 1.13).
  • Vitamin C in one trial of 7627 women: higher lung cancer incidence, RR 1.84 (95% CI 1.14 to 2.95).
  • Vitamin E: no difference in lung cancer incidence (RR 1.01, 95% CI 0.90 to 1.14; 3 trials, 36841 participants).
  • Vitamin E in one trial of 14641 male physicians: more haemorrhagic strokes (39 versus 23 events), HR 1.74 (95% CI 1.04 to 2.91).
  • Vitamin D plus calcium in postmenopausal women (3 trials, 37601 women): no difference in lung cancer incidence, RR 0.90 (95% CI 0.39 to 2.08).
  • Selenium in one trial of 17448 men: no difference in lung cancer incidence, RR 1.11 (95% CI 0.80 to 1.54).
  • Vitamins A, C and E plus selenium plus zinc in one trial of 12741 participants: no difference in lung cancer incidence, RR 0.64 (95% CI 0.28 to 1.48).
• The authors' conclusion: The authors concluded there was no evidence that supplements of vitamins A, C, E, D or selenium, alone or combined, prevent lung cancer or lung cancer mortality in healthy people. They also concluded that some supplements may harm some groups: in smokers and people exposed to asbestos, vitamin A increases lung cancer incidence, lung cancer mortality and all-cause mortality; vitamin C increases lung cancer incidence in women; and vitamin E increases the risk of haemorrhagic strokes.
• Limitations the authors state:
  • Publication bias could not be assessed with funnel plots because each comparison had five or fewer studies.
  • Small studies, especially older ones, may have been missed.
  • The vitamin C finding in women should be taken with caution: it comes from a single study, and the difference was not statistically significant for men or for men and women pooled.
  • Four of the included studies did not give the information needed to assess risk of bias in some domains.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, confidence interval, Hazard Ratio.

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