Martin Lipkin

Vitamin D status differs by latitude and race, with residents of the northeastern United States and individuals with more skin pigmentation being at increased risk of deficiency. A PubMed database search yielded 63 observational studies of vitamin D status in relation to cancer risk, including 30 of colon, 13 of breast, 26 of prostate, and 7 of ovarian cancer, and several that assessed the association of vitamin D receptor genotype with cancer risk. The majority of studies found a protective relationship between sufficient vitamin D status and lower risk of cancer. The evidence suggests that efforts to improve vitamin D status, for example by vitamin D supplementation, could reduce cancer incidence and mortality at low cost, with few or no adverse effects.

The gastrointestinal tract is lined by a layer of mucus comprised of highly glycosylated proteins called mucins. To evaluate the importance of mucin in intestinal carcinogenesis, we constructed mice genetically deficient in Muc2, the most abundant secreted gastrointestinal mucin. Muc2-/- mice displayed aberrant intestinal crypt morphology and altered cell maturation and migration. Most notably, the mice frequently developed adenomas in the small intestine that progressed to invasive adenocarcinoma, as well as rectal tumors. Thus, Muc2 is involved in the suppression of colorectal cancer.

We studied the frequency and distribution of proliferating epithelial cells lining colonic crypts in 10 subjects at high risk for familial colonic cancer, before and after oral supplementation of their conventional diets with 1.25 g of calcium as calcium carbonate. Patterns of cell proliferation were defined by dividing the colonic crypt into longitudinal compartments and comparing the numbers and fractions of tritiated thymidine--labeled epithelial cells in the various compartments. Before dietary supplementation with calcium, the profile of proliferating epithelial cells in the colonic crypts was comparable to that previously observed in subjects who had had familial colonic cancer. Two to three months after supplementation had been started, proliferation was significantly reduced and the profile of the colonic crypts approached that previously observed in subjects at low risk for colonic cancer. Our findings indicate that oral calcium supplementation induces a more quiescent equilibrium in epithelial-cell proliferation in the colonic mucosa of subjects at high risk of colon cancer, similar to that observed in subjects at low risk.