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Convincing evidence is available showing that dietary calcium and vitamin D impede the development of colonic carcinogenesis. The major cellular modes of action of calcium and vitamin D which can contribute to the inhibition of colonic neoplasia are reviewed in this article. These consist of complex series of signaling events induced by the chemopreventive agents acting at various tiers of colonic cell organization.

Loss of function of the adenomatous polyposis coli (APC) tumor suppressor gene predisposes for familial adenomatous polyposis (FAP) syndrome. The Apc gene knockout mice exhibit accelerated intestinal carcinogensis modifiable by diverse pharmacological agents. Present experiments utilized the Apc[+/-] 1638N COL colon epithelial cell line (origin: histologically normal colon) as the model. Retinoid receptor modulator 9-cis-retinoic acid (9-cis-RA), ornithine decarboxylase inhibitor difluoromethyl ornithine (DFMO), and nonselective cyclooxygenase inhibitor sulindac (SUL) represented the chemopreventive test compounds. Population doubling, cell cycle progression, and anchorage-independent growth provided mechanistic end points for chemopreventive efficacy. Treatment of 1638N COL cells with 9-cis-RA, DFMO and SUL produced a dose-dependent cytostatic growth arrest by decreasing the number of population doublings and altering aneuploid G0/G1:S+G2/M ratio. The clonally expanded 1638N-Cl1 cells selected for anchorage-independent growth exhibited decreased anchorage-independent colony formation in response to treatment with the three test compounds. Susceptibility of preneoplastic 1638N COL cells to mechanistically distinct chemopreventive agents validates a unique epithelial cell culture model for FAP syndrome, and facilitates investigations on Apc regulated colon carcinogenesis and cancer prevention.

Cyclooxygenase (COX) catalyzes the formation of prostaglandins (PG) from arachidonic acid. A large body of evidence has accumulated to suggest that COX-2, the inducible form of COX, is important in carcinogenesis. In this study, we determined whether (1) COX-2 was overexpressed in squamous cell carcinoma of the head and neck (HNSCC) and whether (2) retinoids, a class of chemopreventive agents, blocked epidermal growth factor (EGF)-mediated activation of COX-2 expression. Levels of COX-2 mRNA were determined in 15 cases of HNSCC and 10 cases of normal oral mucosa. Nearly a 100-fold increase in amounts of COX-2 mRNA was detected in HNSCC. By immunoblot analysis, COX-2 protein was detected in 6 of 6 cases of HNSCC but was undetectable in normal mucosa. Because retinoids protect against oral cavity cancer, we investigated whether retinoids could suppress EGF-mediated induction of COX-2 in cultured oral squamous carcinoma cells. Treatment with EGF led to increased levels of COX-2 mRNA, COX-2 protein, and synthesis of PG. These effects were suppressed by a variety of retinoids. Based on the results of this study, it will be important to establish whether newly developed selective COX-2 inhibitors are useful in preventing or treating HNSCC. Moreover, the anticancer properties of retinoids may be due, in part, to inhibition of COX-2 expression. Combining a retinoid with a selective COX-2 inhibitor may be more effective than either agent alone in preventing cancer of the upper aerodigestive tract.

Experimental studies in animals and epidemiological studies in human populations support an inverse association between exercise and the development of cancer. Physical activity has been shown to be protective against the development of breast and colon cancer and may also be important for other kinds of cancer such as that of the prostate. The proposed biological mechanisms for the physical activity--cancer association include exercise's effect on immune function, transit time of digestion, hormones, and body fat. There has been little research on physical activity and the effect on progression of cancer, although there are studies to suggest that it may slow the clinical course of the disease. Furthermore, exercise may be beneficial in the treatment of cancer through mood elevation, decreased loss of lean tissue, and increased quality of life. Much is still to be learned about the effect of exercise on cancer. The intensity, duration, frequency, and type of exercise that is relevant need to be clarified. As well, the time period during life when exercise is important has not been determined. It seems reasonable to conclude that exercise, a modifiable risk factor, is beneficial in preventing certain forms of cancer. Public health interventions may hold promise for cancer prevention.

In summary, we need to provide fully informed consent regarding the hazards and the benefits of genetic testing and defining risk. This reflects the first ethical principle of autonomy. It is the responsibility of the counseling team to make sure that the individual is psychologically equipped to deal with the emotional distress that may result from testing. An undue burden must not be placed on someone and harm must not be inflicted. This is the second ethical principle of beneficence. Third, awareness of the potential problems of testing is extremely important. These issues are those of disclosure, insurance problems, and employment problems--the third ethical principle of confidentiality. Recommendations for screening guidelines, regardless of testing results, should be provided. It is important for women who are not gene carriers to know that they still need to go for screening. Lastly, we need to find ways to help individuals cope with their risk status, whether it is actual high risk or perceived high risk. Helping women to develop positive coping strategies and to adhere to screening is extremely important. As the Huntington's data indicated, over time, regardless of their risk levels, individuals do learn how to cope and adapt with the outcome of testing. Women and men need to learn how to live with their risk status so that the negative psychological sequelae will be minimized.