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

Authors

  • Chun Liu MD,

    Corresponding author
    1. Nutrition and Cancer Biology Laboratory, US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts
    • USDA Human Nutrition Research Center on Aging at Tufts University, 711 Washington Street, Boston, MA 02111===

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    • Fax: (617) 556-3344

  • Xiang-Dong Wang MD, PhD,

    1. Nutrition and Cancer Biology Laboratory, US Department of Agriculture Human Nutrition Research Center on Aging at Tufts University, Boston, Massachusetts
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  • Lorelei Mucci ScD,

    1. Channing Laboratory, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • J. Michael Gaziano MD,

    1. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
    2. Division of Aging, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • Shumin M. Zhang MD, ScD

    1. Division of Preventive Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts
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  • We are indebted to the participants in the Physicians' Health Study for their dedicated and conscientious collaboration; to Eduardo Pereira for his statistical analytic support; to Melissa Aquino, Julia Fleet, and the entire staff of the Physicians' Health Study for their assistance in the study; to Ella Litvak and Vadim Budes for the technical assistance with the article; and to Drs. Ute Obermueller-Jevic and Klaus Kraemer from the BASF Chemical Company for their support for the study.

Abstract

BACKGROUND:

β-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 β-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 β (RARβ), 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 β-carotene treatment assignment and other characteristics using unconditional logistic regression models.

RESULTS:

The positivity for total p53, RARβ, cyclin D1, and PCNA was nonsignificantly lower among lung cancer patients who were assigned to receive β-carotene than those who were assigned to receive β-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 β-carotene and men who received β-carotene placebo.

CONCLUSIONS:

The 50-mg β-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 β-carotene, which demonstrated no benefit or harm to the risk of developing lung cancer. Cancer 2009. © 2009 American Cancer Society.

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