Calcium plus vitamin D alters preneoplastic features of colorectal adenomas and rectal mucosa

Authors

  • Peter R. Holt M.D.,

    1. Department of Medicine, St. Luke's/Roosevelt Hospital Center, Columbia University, New York, New York
    Current affiliation:
    1. Strang Cancer Prevention Center, New York, New York
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    • The first two authors contributed equally to this project.

  • Robert S. Bresalier M.D.,

    Corresponding author
    1. Department of Gastrointestinal Medicine and Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
    • Department of Gastrointestinal Medicine and Nutrition, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 436, Houston, TX 77459
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    • The first two authors contributed equally to this project.

    • Fax: (713) 745-9295

  • Chan K. Ma M.D.,

    1. Department of Pathology, Henry Ford Hospital, Detroit, Michigan
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  • Kai-Feng Liu M.D.,

    1. Department of Gastrointestinal Medicine and Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Martin Lipkin M.D.,

    1. Strang Cancer Prevention Center, New York, New York
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  • James C. Byrd Ph.D.,

    1. Department of Gastrointestinal Medicine and Nutrition, The University of Texas M. D. Anderson Cancer Center, Houston, Texas
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  • Kan Yang M.D.

    1. Strang Cancer Prevention Center, New York, New York
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Abstract

BACKGROUND

Calcium and vitamin D are chemopreventive agents for colorectal neoplasia. Studies of the effects of calcium and vitamin D on early surrogate markers of reduced risk, such as proliferation, have been limited to evaluation of the flat colorectal mucosa. Biologic changes that may occur in colorectal adenomas after chemopreventive regimens have not been reported.

METHODS

In the current study, adenomatous polyps were transected, approximately 50% were removed for histologic examination, and the remnants tattooed before the administration of either calcium carbonate (1500 mg 3 times daily) plus vitamin D3 400 IU or a placebo for 6 months. At study end, polyp remnants were resected completely and were used for histologic examination. Immunohistochemical staining was performed in both flat mucosa and in polyp tissue. Proliferation was assessed by MIB-1 staining; apoptosis was assessed by terminal deoxyuridine triphosphate-biotin nick-end labeling, BAK, and Bcl-2 staining; and cytokeratin AE1, vitamin D receptor, MUC5AC mucin, and galectin-3 were assessed by immunohistochemisty.

RESULTS

Nineteen patients, including 11 patients in the treatment group and 8 patients in the control group, completed the study. Proliferative indices fell both in flat mucosa and in polyps in the treatment group, and there were no significant changes in the control group. Apoptosis and Bcl-2 immunostaining were unchanged in both groups, but the frequency of BAK-immunostained cells in the interior of polyps rose significantly. Vitamin D receptor staining increased slightly and significantly in flat rectal tissue in the treatment group. There were no significant changes in galectin-3 staining, but a striking reduction in MUC5AC mucin staining in polyps was observed after treatment with calcium plus vitamin D.

CONCLUSIONS

The administration of a calcium plus vitamin D chemopreventive regimen resulted in several changes in adenomatous tissue that may have contributed to reduced polyp formation. Cancer 2006. © 2005 American Cancer Society.

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