Modulation of lung molecular biomarkers by beta-carotene in the Physicians' Health Study

Cancer. 2009 Mar 1;115(5):1049-58. doi: 10.1002/cncr.24061.


Background: Beta-Carotene supplementation showed neither benefit nor harm among apparently healthy physicians (all men) in the Physicians' Health Study (PHS) trial. The objective of the current investigation was to evaluate how long-term beta-carotene supplementation affects molecular markers of lung carcinogenesis in the PHS.

Methods: The protein levels of total p53, cyclin D1, proliferating cellular nuclear antigen (PCNA), retinoic acid receptor beta (RARbeta), and cytochrome p450 enzyme 1A1 (CYP1A1) were measured using the immunohistochemical method in 40 available archival lung tissue samples from patients who were diagnosed with lung cancer in the PHS. The protein levels of these markers were compared by category of beta-carotene treatment assignment and other characteristics using unconditional logistic regression models.

Results: The positivity for total p53, RARbeta, cyclin D1, and PCNA was nonsignificantly lower among lung cancer patients who were assigned to receive beta-carotene than those who were assigned to receive beta-carotene placebo. There was a borderline significant difference in CYP1A1 positivity with an OR of 0.2 (95% confidence interval, 0.2-1.1; P = .06) in a comparison of men who received beta-carotene and men who received beta-carotene placebo.

Conclusions: The 50-mg beta-carotene supplementation on alternate days had no significant influence on molecular markers of lung carcinogenesis that were evaluated in the PHS. This finding provides mechanistic support for the main PHS trial results of beta-carotene, which demonstrated no benefit or harm to the risk of developing lung cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism*
  • Dietary Supplements*
  • Female
  • Humans
  • Immunohistochemistry
  • Lung Neoplasms / metabolism*
  • Male
  • Middle Aged
  • Randomized Controlled Trials as Topic
  • beta Carotene / pharmacology*


  • Biomarkers
  • beta Carotene