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Cited by 1,255Antioxidant Activity and Oxidative StressLung Cancer Diagnosis and TreatmentRetinoids in leukemia and cellular processes

The DOI matches its Crossref record; 1 of the 1 references it cites were found in a registry or an index.

Risk Factors for Lung Cancer and for Intervention Effects in CARET, the Beta-Carotene and Retinol Efficacy Trial

Open access
Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F. L., Valanis, B., Williams, J. H., Barnhart, S., Cherniack, M. G., Brodkin, C. A., Hammar, S.·1996·JNCI Journal of the National Cancer Institute
DOI 10.1093/jnci/88.21.1550
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Abstract

BACKGROUND: Evidence has accumulated from observational studies that people eating more fruits and vegetables, which are rich in beta-carotene (a violet to yellow plant pigment that acts as an antioxidant and can be converted to vitamin A by enzymes in the intestinal wall and liver) and retinol (an alcohol chemical form of vitamin A), and people having higher serum beta-carotene concentrations had lower rates of lung cancer. The Beta-Carotene and Retinol Efficacy Trial (CARET) tested the combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate (vitamin A) taken daily against placebo in 18314 men and women at high risk of developing lung cancer. The CARET intervention was stopped 21 months early because of clear evidence of no benefit and substantial evidence of possible harm; there were 28% more lung cancers and 17% more deaths in the active intervention group (active = the daily combination of 30 mg beta-carotene and 25,000 IU retinyl palmitate). Promptly after the January 18, 1996, announcement that the CARET active intervention had been stopped, we published preliminary findings from CARET regarding cancer, heart disease, and total mortality. PURPOSE: We present for the first time results based on the pre-specified analytic method, details about risk factors for lung cancer, and analyses of subgroups and of factors that possibly influence response to the intervention. METHODS: CARET was a randomized, double-blinded, placebo-controlled chemoprevention trial, initiated with a pilot phase and then expanded 10-fold at six study centers. Cigarette smoking history and status and alcohol intake were assessed through participant self-report. Serum was collected from the participants at base line and periodically after randomization and was analyzed for beta-carotene concentration. An Endpoints Review Committee evaluated endpoint reports, including pathologic review of tissue specimens. The primary analysis is a stratified logrank test for intervention arm differences in lung cancer incidence, with weighting linearly to hypothesized full effect at 24 months after randomization. Relative risks (RRs) were estimated by use of Cox regression models; tests were performed for quantitative and qualitative interactions between the intervention and smoking status or alcohol intake. O'Brien-Fleming boundaries were used for stopping criteria at interim analyses. Statistical significance was set at the .05 alpha value, and all P values were derived from two-sided statistical tests. RESULTS: According to CARET's pre-specified analysis, there was an RR of 1.36 (95% confidence interval [CI] = 1.07-1.73; P = .01) for weighted lung cancer incidence for the active intervention group compared with the placebo group, and RR = 1.59 (95% CI = 1.13-2.23; P = .01) for weighted lung cancer mortality. All subgroups, except former smokers, had a point estimate of RR of 1.10 or greater for lung cancer. There are suggestions of associations of the excess lung cancer incidence with the highest quartile of alcohol intake (RR = 1.99; 95% CI = 1.28-3.09; test for heterogeneity of RR among quartiles of alcohol intake has P = .01, unadjusted for multiple comparisons) and with large-cell histology (RR = 1.89; 95% CI = 1.09-3.26; test for heterogeneity among histologic categories has P = .35), but not with base-line serum beta-carotene concentrations. CONCLUSIONS: CARET participants receiving the combination of beta-carotene and vitamin A had no chemopreventive benefit and had excess lung cancer incidence and mortality. The results are highly consistent with those found for beta-carotene in the Alpha-Tocopherol Beta-Carotene Cancer Prevention Study in 29133 male smokers in Finland.

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Crossref · 10.1093/jnci/88.21.1550

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  • In smokers, high doses of beta-carotene were associated with a higher incidence of lung cancer and mortality rate.

    “Nevertheless, adverse health effects concerning carotenoids have been reported in smokers who had a higher incidence of lung cancer and mortality rate after high doses of beta-carotene [1,10,20,21,22].”

    From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [21]

  • Regular use of AREDS2 has been shown to reduce the risk of developing severe AMD.

    “Regular use of AREDS2 has been shown to reduce the risk of developing severe AMD [21,22,23].”

    From The Role of Vitamin A in Retinal Diseases (2022) · cites this paper as [21]

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Metadata

Authors
Omenn, G. S., Goodman, G. E., Thornquist, M. D., Balmes, J., Cullen, M. R., Glass, A., Keogh, J. P., Meyskens, F. L., Valanis, B., Williams, J. H., Barnhart, S., Cherniack, M. G., Brodkin, C. A., & Hammar, S.
Affiliations
  • University of Washington (US)
  • Fred Hutch Cancer Center (US)
  • University of California, San Francisco (US)
  • Yale University (US)
  • Kaiser Permanente (US)
  • University of Maryland, Baltimore (US)
  • University of California, Irvine (US)
Corresponding author
Omenn, G. S.
ORCID
Venue
JNCI Journal of the National Cancer Institute
Publisher
Oxford University Press (OUP)
Published
1996-11-06
Volume
88
Issue
21
Pages
1550-1559
ISSN
  • 0027-8874 (ISSN-L)
  • 1460-2105
DOI
10.1093/jnci/88.21.1550
OpenAlex
W2153399329
Cited by
1,255
References
1
Citations by year
2026: 14 · 2025: 16 · 2024: 19 · 2023: 28 · 2022: 35 · 2021: 37 · 2020: 34 · 2019: 26 · 2018: 37 · 2017: 33 · 2016: 35 · 2015: 47 · 2014: 50 · 2013: 50 · 2012: 59
FWCI
24.64
Type
journal article
Language
en
Open access
Locations
  • JNCI Journal of the National Cancer Institute (publishedVersion)
  • PubMed (publishedVersion)
  • eScholarship (California Digital Library) (submittedVersion, cc-by)
Funders
  • National Institutes of Health (1u01ca063674-01)
  • National Cancer Institute (U01 CA 63673, U01CA47988, U01 CA63674, U01CA063673)
Topics
  • Health Sciences › Medicine › Biochemistry (medical) › Antioxidant Activity and Oxidative Stress
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Lung Cancer Diagnosis and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Retinoids in leukemia and cellular processes
Keywords
lung cancer, beta-carotene, retinol, CARET trial, chemoprevention, vitamin A, risk factors, smoking, alcohol consumption, serum beta-carotene, interaction effects, lung cancer incidence, lung cancer mortality, subgroup analysis, antioxidant supplementation, all-cause mortality, men and women
MeSH terms
Retinyl Esters, Antioxidants, Asbestos, Carcinogens, Diterpenes, Double-Blind Method, Drug Therapy, Combination, Female, Humans, Lung Neoplasms, Male, Risk Factors, Smoking, Vitamin A, Proportional Hazards Models, Anticarcinogenic Agents, beta Carotene

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