MEDICAL HYPOTHESES AND RESEARCH
VOL. 1, No. 2 / 3, July 2004


H. L. Newmark and N. Suh [2004] Med Hypotheses Res 1: 67-75.

Mechanistic Hypothesis for the Interaction of Dietary
Fat, Calcium, and Vitamin D in Breast Cancer


Harold L. Newmark* and Nanjoo Suh

Susan Lehman Cullman Laboratory for Cancer Research, Department of Chemical
Biology, Rutgers  The State University of New Jersey, Piscataway, New Jersey 08854,
USA


Abstract. High dietary fat is one of several factors correlated with increased
incidence of breast cancer in inter-country population studies. Laboratory animal studies
suggest that high dietary fat acts as a promoter of chemical carcinogen-induced mammary
cancer, and high fat diet increases epithelial cell proliferation of the mammary ducts,
particularly in the small terminal ducts. The hypothesis proposes that high fat diet
increases fat secretion into the small ducts leading from the terminal end buds. In non-
lactating women, particularly nullaporous women, a milk-like fluid, moving very slowly in
the duct can be partly metabolized, producing long chain free fatty acids (FFA's) from the
secreted fat. These FFA's can be highly cytotoxic to local epithelial cells, resulting in cell
damage and necrosis, followed by increased cell proliferation. The mechanism of FFA
cytotoxicity has been studied in the colon, and shown to be related to the potent
sequestration of calcium from the cells by the FFA's. In the colon, increased dietary
calcium can readily prevent colon lumenal FFA's from these cytotoxic and
hyperproliferative effects. In the breast, increase of local calcium availability from the
systemic circulation depends to a greater extent on availability of calcitriol, the active
metabolite of vitamin D. An inverse epidemiological correlation has been developed
between sunlight availability as a source of vitamin D and the risk of breast cancer in the
U.S. and Canada. A large scale prospective observation study in over 88,000 women for 16
years (the Nurses Health Study) lends support to this hypothesis. Reduction of breast
cancer risk, and simultaneously osteoporosis, might be achieved by increasing dietary
intake of calcium and vitamin D. This may be particularly applicable to females during
puberty and adolescence.


*Address all correspondence to: Dr. Harold L. Newmark, Susan Lehman Cullman
Laboratory for Cancer Research, Department of Chemical Biology, Rutgers  The State
University of New Jersey, 164 Frelinghuysen Road, Piscataway, NJ 08854 (USA).


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