Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1993 Mar;67(3):500–503. doi: 10.1038/bjc.1993.93

Epithelial cell proliferation in the sigmoid colon of patients with adenomatous polyps increases during oral calcium supplementation.

J H Kleibeuker 1, J W Welberg 1, N H Mulder 1, R van der Meer 1, A Cats 1, A J Limburg 1, W M Kreumer 1, M J Hardonk 1, E G de Vries 1
PMCID: PMC1968268  PMID: 8439500

Abstract

To study the effect of oral supplemental calcium on colonic epithelial proliferation, 17 adenomatous polyp patients received 1.5 g Ca2+ as calcium carbonate daily during 12 weeks, while on a calcium constant diet, based on the patients' habitual diet. Seven subsequently continued calcium supplementation for 9 months without dietary restrictions. Epithelial proliferation rate in colonic biopsies, expressed as labelling index (%), was determined with 5-bromodeoxyuridine and immunohistochemistry. Biopsies were taken from the midsigmoid at time of polyp excision and at the end of the intervention period. Median labelling index increased from 6.1% before to 8.7% after 12 weeks calcium (n = 17, P < 0.02). This was due to increased labelling in the basal third of the crypts (11.9 vs 16%), whereas labelling in mid and luminal compartments was not affected. Labelling index remained increased after 1 year calcium supplementation at 8.8%. Crypt length was not affected by calcium. These results are in contrast to those of others, who have shown a decrease of rectal epithelial proliferation during similar doses of calcium. Therefore, the effect of nutritional intervention on colonic epithelial proliferation should be studied in biopsies taken not only from the rectum, but also from more proximal parts of the colon. Caution with respect to large scale intervention studies with calcium in high risk groups is mandatory.

Full text

PDF
500

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Barsoum G. H., Hendrickse C., Winslet M. C., Youngs D., Donovan I. A., Neoptolemos J. P., Keighley M. R. Reduction of mucosal crypt cell proliferation in patients with colorectal adenomatous polyps by dietary calcium supplementation. Br J Surg. 1992 Jun;79(6):581–583. doi: 10.1002/bjs.1800790639. [DOI] [PubMed] [Google Scholar]
  2. Garland C., Shekelle R. B., Barrett-Connor E., Criqui M. H., Rossof A. H., Paul O. Dietary vitamin D and calcium and risk of colorectal cancer: a 19-year prospective study in men. Lancet. 1985 Feb 9;1(8424):307–309. doi: 10.1016/s0140-6736(85)91082-7. [DOI] [PubMed] [Google Scholar]
  3. Gregoire R. C., Stern H. S., Yeung K. S., Stadler J., Langley S., Furrer R., Bruce W. R. Effect of calcium supplementation on mucosal cell proliferation in high risk patients for colon cancer. Gut. 1989 Mar;30(3):376–382. doi: 10.1136/gut.30.3.376. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Heilbrun L. K., Hankin J. H., Nomura A. M., Stemmermann G. N. Colon cancer and dietary fat, phosphorus, and calcium in Hawaiian-Japanese men. Am J Clin Nutr. 1986 Feb;43(2):306–309. doi: 10.1093/ajcn/43.2.306. [DOI] [PubMed] [Google Scholar]
  5. Kune S., Kune G. A., Watson L. F. Case-control study of dietary etiological factors: the Melbourne Colorectal Cancer Study. Nutr Cancer. 1987;9(1):21–42. doi: 10.1080/01635588709513908. [DOI] [PubMed] [Google Scholar]
  6. Lipkin M., Friedman E., Winawer S. J., Newmark H. Colonic epithelial cell proliferation in responders and nonresponders to supplemental dietary calcium. Cancer Res. 1989 Jan 1;49(1):248–254. [PubMed] [Google Scholar]
  7. Lipkin M., Newmark H. Effect of added dietary calcium on colonic epithelial-cell proliferation in subjects at high risk for familial colonic cancer. N Engl J Med. 1985 Nov 28;313(22):1381–1384. doi: 10.1056/NEJM198511283132203. [DOI] [PubMed] [Google Scholar]
  8. McNeil N. I., Rampton D. S. Is the rectum usually empty?--A quantitative study in subjects with and without diarrhea. Dis Colon Rectum. 1981 Nov-Dec;24(8):596–599. doi: 10.1007/BF02605753. [DOI] [PubMed] [Google Scholar]
  9. Negri E., La Vecchia C., D'Avanzo B., Franceschi S. Calcium, dairy products, and colorectal cancer. Nutr Cancer. 1990;13(4):255–262. doi: 10.1080/01635589009514067. [DOI] [PubMed] [Google Scholar]
  10. Newmark H. L., Wargovich M. J., Bruce W. R. Colon cancer and dietary fat, phosphate, and calcium: a hypothesis. J Natl Cancer Inst. 1984 Jun;72(6):1323–1325. [PubMed] [Google Scholar]
  11. Risio M., Lipkin M., Candelaresi G., Bertone A., Coverlizza S., Rossini F. P. Correlations between rectal mucosa cell proliferation and the clinical and pathological features of nonfamilial neoplasia of the large intestine. Cancer Res. 1991 Apr 1;51(7):1917–1921. [PubMed] [Google Scholar]
  12. Rozen P., Fireman Z., Fine N., Wax Y., Ron E. Oral calcium suppresses increased rectal epithelial proliferation of persons at risk of colorectal cancer. Gut. 1989 May;30(5):650–655. doi: 10.1136/gut.30.5.650. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Scalmati A., Roncucci L., Ghidini G., Biasco G., Ponz de Leon M. Epithelial cell kinetics in the remaining colorectal mucosa after surgery for cancer of the large bowel. Cancer Res. 1990 Dec 15;50(24):7937–7941. [PubMed] [Google Scholar]
  14. Slattery M. L., Sorenson A. W., Ford M. H. Dietary calcium intake as a mitigating factor in colon cancer. Am J Epidemiol. 1988 Sep;128(3):504–514. doi: 10.1093/oxfordjournals.aje.a114998. [DOI] [PubMed] [Google Scholar]
  15. Stern H. S., Gregoire R. C., Kashtan H., Stadler J., Bruce R. W. Long-term effects of dietary calcium on risk markers for colon cancer in patients with familial polyposis. Surgery. 1990 Sep;108(3):528–533. [PubMed] [Google Scholar]
  16. Terpstra O. T., van Blankenstein M., Dees J., Eilers G. A. Abnormal pattern of cell proliferation in the entire colonic mucosa of patients with colon adenoma or cancer. Gastroenterology. 1987 Mar;92(3):704–708. doi: 10.1016/0016-5085(87)90021-7. [DOI] [PubMed] [Google Scholar]
  17. Thornton J. R. High colonic pH promotes colorectal cancer. Lancet. 1981 May 16;1(8229):1081–1083. doi: 10.1016/s0140-6736(81)92244-3. [DOI] [PubMed] [Google Scholar]
  18. Van der Meer R., Welberg J. W., Kuipers F., Kleibeuker J. H., Mulder N. H., Termont D. S., Vonk R. J., De Vries H. T., De Vries E. G. Effects of supplemental dietary calcium on the intestinal association of calcium, phosphate, and bile acids. Gastroenterology. 1990 Dec;99(6):1653–1659. doi: 10.1016/0016-5085(90)90471-c. [DOI] [PubMed] [Google Scholar]
  19. Walker A. R., Walker B. F., Walker A. J. Faecal pH, dietary fibre intake, and proneness to colon cancer in four South African populations. Br J Cancer. 1986 Apr;53(4):489–495. doi: 10.1038/bjc.1986.77. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Wargovich M. J., Isbell G., Shabot M., Winn R., Lanza F., Hochman L., Larson E., Lynch P., Roubein L., Levin B. Calcium supplementation decreases rectal epithelial cell proliferation in subjects with sporadic adenoma. Gastroenterology. 1992 Jul;103(1):92–97. doi: 10.1016/0016-5085(92)91100-i. [DOI] [PubMed] [Google Scholar]
  21. Weisburger J. H., Wynder E. L. Etiology of colorectal cancer with emphasis on mechanism of action and prevention. Important Adv Oncol. 1987:197–220. [PubMed] [Google Scholar]
  22. Welberg J. W., de Vries E. G., Hardonk M. J., Mulder N. H., Harms G., Grond J., Zwart N., Koudstaal J., de Ley L., Kleibeuker J. H. Proliferation rate of colonic mucosa in normal subjects and patients with colonic neoplasms: a refined immunohistochemical method. J Clin Pathol. 1990 Jun;43(6):453–456. doi: 10.1136/jcp.43.6.453. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Ziegler R. G., Devesa S. S., Fraumeni J. F., Jr Epidemiologic patterns of colorectal cancer. Important Adv Oncol. 1986:209–232. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES