Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers

Our plain-English summary of Estimated intake of vitamin D and its interaction with vitamin A on lung cancer risk among smokers, by T.Y. Cheng, G.E. Goodman, M.D. Thornquist, et al (International Journal of Cancer, 2014).

The study

• Authors: T.Y. Cheng, G.E. Goodman, M.D. Thornquist, M.J. Barnett, S.A. Beresford, A.Z. LaCroix, Y. Zheng, M.L. Neuhouser
• Journal: International Journal of Cancer
• Published: 2014;135(9):2135-45
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Data are very limited on vitamin D and lung cancer prevention in high-risk populations. The authors investigated whether estimated vitamin D intake was associated with lung cancer risk and whether effect modification by vitamin A existed among current/former heavy smokers and workers with occupational exposure to asbestos. A case-cohort study selected 749 incident lung cancers and 679 noncases from the Carotene and Retinol Efficacy Trial (CARET), 1988-2005. The active intervention was supplementation of 30 mg β-carotene + 25,000 IU retinyl palmitate/day. Baseline total intake including both diet (from food frequency questionnaire) and personal supplements (from brand names linked to the labeled potencies) was assessed. Hazard ratios (HRs) were estimated by Cox proportional hazard models. No significant association of total vitamin D intake with lung cancer was observed overall. However, total vitamin D intake ≥600 versus <200 IU/day was associated with a lower risk of non-small cell lung cancer among former smokers [HR = 0.36, 95% confidence interval (CI) = 0.13-0.96]. Total vitamin D intake ≥400 versus <400 IU/day was associated with a lower risk of total lung cancer among participants who received the CARET active intervention (HR = 0.56, 95% CI = 0.32-0.99) and among those who had total vitamin A intake ≥1,500 µg/day retinol activity equivalent (RAE; HR = 0.46, 95% CI = 0.23-0.91). The beneficial associations were attenuated among those who did not receive the CARET active intervention or who had total vitamin A intake <1,500 µg/day RAE (p-interaction = 0.02 for current smokers). Our observation suggests that vitamin A may assist vitamin D in preventing lung cancer among smokers.

© 2014 UICC.

In plain English

This case–cohort study used CARET, a U.S. lung cancer prevention trial of heavy smokers and asbestos-exposed workers (1988–2005). It compared 749 people who developed lung cancer with 679 who did not, by estimated baseline vitamin D intake from food and supplements. Overall, intake was not significantly associated with lung cancer. Among former smokers, 600 IU/day or more versus under 200 IU/day was associated with lower risk of non-small cell lung cancer (hazard ratio 0.36, 95% CI 0.13–0.96). Intake of 400 IU/day or more versus less was associated with lower lung cancer risk among people receiving the trial's beta-carotene plus vitamin A supplements (HR 0.56, 95% CI 0.32–0.99) and among those whose diet and personal supplements supplied at least 1,500 micrograms/day retinol activity equivalents of vitamin A (HR 0.46, 95% CI 0.23–0.91). Neither appeared in the comparison groups, though tests for a group difference were not significant in the analysis of all participants. The authors concluded that vitamin A may assist vitamin D in preventing lung cancer among smokers, warning that borderline results could be chance. Asbestos exposure was adjusted for but not itself studied.

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: Case–cohort study within a randomized chemoprevention trial (CARET), analyzed with Cox proportional hazards models
• Who was studied: 749 incident lung cancer cases (including 44 who were also in the random subcohort) and 679 noncases from CARET, 1988–2005. CARET enrolled heavy current or former smokers and men exposed to asbestos at work. The analysis covered centers in Seattle, Irvine, New Haven, San Francisco and Baltimore; Portland was excluded. 208 cases (27.8%) and 193 noncases (28.4%) were enrolled as asbestos exposure workers.
• Exposure: Estimated baseline total vitamin D intake (diet from a food frequency questionnaire plus personal supplements from brand-name labels). Effect modification was examined by the CARET active intervention (30 mg beta-carotene plus 25,000 IU retinyl palmitate daily, versus placebo) and by total vitamin A intake from food and personal supplements, expressed as retinol activity equivalents (RAE). Asbestos exposure was not the exposure studied; enrollment as an asbestos worker and years in asbestos trade were adjusted for.
• Main results:
  • No significant association of total vitamin D intake with lung cancer overall (all participants; also none among current smokers per the article's Table 2).
  • Former smokers with 800 IU/day or more versus under 200 IU/day had a 74% lower lung cancer risk, but this was not statistically significant (HR 0.26, 95% CI 0.06–1.09; p-trend 0.06).
  • Among former smokers, total vitamin D intake of 600 IU/day or more versus under 200 IU/day was associated with lower risk of non-small cell lung cancer: HR 0.36, 95% CI 0.13–0.96.
  • Among participants who received the CARET active intervention, vitamin D intake of 400 IU/day or more versus under 400 IU/day was associated with lower lung cancer risk: HR 0.56 (95% CI 0.32–0.99) for all participants and HR 0.25 (95% CI 0.08–0.76) for former smokers.
  • This inverse association was not seen among participants who did not receive the CARET active intervention (HR 1.07, 95% CI 0.75–1.54, all participants, per Table 4).
  • Among all participants whose total vitamin A intake from food and personal supplements (not counting the CARET intervention) was at least 1,500 micrograms/day retinol activity equivalents (RAE), vitamin D intake of 400 IU/day or more versus less was associated with lower lung cancer risk (HR 0.46, 95% CI 0.23–0.91). No such association was found among those with vitamin A intake under 1,500 micrograms/day RAE.
  • For all participants, the tests of whether the vitamin D association differed between groups were not statistically significant: p-interaction 0.26 for the CARET active intervention and 0.08 for total vitamin A intake (Table 4).
  • The vitamin D–lung cancer association differed significantly by total vitamin A intake among current smokers (p-interaction 0.02).
• The authors' conclusion: The authors concluded that high total vitamin D intake is associated with a lower risk of non-small cell lung cancer among CARET former smokers, and that vitamin A intake from diet and supplements may assist vitamin D in preventing lung cancer among smokers.
• Limitations the authors state:
  • Several subgroup and stratified associations were borderline significant; larger studies are needed to rule out chance findings.
  • No validation data were available for the questionnaire-estimated dietary vitamin D intake in CARET.
  • Supplement doses were taken from labels and assumed to be daily intake, and only the baseline assessment was used.
  • These measurement errors might have biased the risk estimates toward the null.
  • Among former smokers, the interaction with the CARET intervention was not statistically significant, which the authors attributed to the small number of lung cancers.
  • The findings may not generalize to other populations, because participants were heavy smokers and/or had occupational asbestos exposure.

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, Occupational Exposure, Cohort Study, Hazard Ratio, Non-Small Cell Lung Cancer, confidence interval.

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