Modulation of Abnormal Colonic Epithelial Cell Proliferation and Differentiation
Modulation of Abnormal Colonic Epithelial Cell Proliferation and Differentiation by Low-Fat Dairy Foods
Abstract & Commentary
Synopsis: Increasing the daily intake of calcium by 1200 mg via low-fat dairy foods in patients at high risk for colonic neoplasia reduced proliferative activity of colonic epithelial cells and normalized markers of cellular differentiation.
Source: Holt PR, et al. JAMA 1998;280:1074-1079.
This study is based on epidemiological observations suggesting an inverse relationship between dietary calcium and vitamin D intake and the incidence of colon cancer. Patients at high risk for colon cancer by virtue of having had adenomatous colonic polyps were recruited and randomized to an increase in dietary calcium or to no change in diet. Calcium intake was increased by 1200 mg daily by drinking milk and eating yogurt, ice cream, and low-fat cheese products. To monitor the response, colonic biopsies were obtained by sigmoidscopy twice before and six and 12 months after initiation of the low-fat dairy food diet. The colonic biopsies were analyzed for proliferation, differentiation, and maturation of the cells. Both men and women were studied. There were 33 subjects in the control arm and 37 in the treatment arm. Holt and colleagues found that the addition of low-fat dairy foods reduced colonic epithelial cell proliferation and increased epithelial cell differentiation and maturation. They interpreted these changes as favoring a decreased risk of colon polyp formation and cancer.
Comment by Sarah L. Berga, MD
The present study addresses the hypothesis that diet can modify the incidence of colorectal cancer. This is an important idea and one that should be familiar to most gynecologists, because we typically perform rectal exams at the time of the annual pelvic exam in older women and we should be discussing with patients the pros and cons of various screening procedures for colon cancer, such as sigmoidoscopy or colonoscopy. Further, recent evidence suggests that hormone replacement therapy (HRT) plays a role in the chemoprevention of colon cancer (Grodstein F, et al. Ann Intern Med 1998;128:705-712). In discussing the risks and benefits of HRT, the topic of chemoprevention of colon cancer may well arise and it is best to know something about what lifestyle habits are most likely to be protective.
At first blush, the present study seems straightforward. It would appear safe to conclude based on this report and others that sufficient intake of dairy foods will not only help retard age-related bone loss, but that it will have the additional benefit of reducing risk of colon cancer. The accompanying editorial points out that this conclusion is somewhat premature because the best end points to follow would be the incidence of colon cancer or at least colonic polyps formation rather than cellular markers (Ahnen DJ, Byers T. JAMA 1998;280:1095-1096). The reason for not using more definitive end points, however, is that it takes much longer to do such a study. Fortunately, another randomized trial followed the relationship between calcium supplementation and colonic polyps (Baron JA, Beach M. Gastroenterology 1998;114:A563; Baron JA, et al. J Natl Cancer Inst 1995;87:1303-1307). That study found that calcium supplementation reduced the rate of new polyp formation but did not change markers of cellular proliferation. In considering the available evidence, Holt and associates suggest that increasing dietary calcium would be expected to reduce the risk of colorectal cancer in those most prone by 5-25%. They also point out that other lifestyle and dietary interventions to reduce colon cancer should be emphasized when addressing the topic of chemoprevention of colon cancer. These factors include smoking, aspirin use, physical activity, fruits and vegetables, and dietary fat.
Rendering preventive health services to older women is a complex task, but one that we must embrace. Women want our opinion. Those who see only a gynecologist depend on us to review general health maintenance. Many insurance plans permit women an annual visit to the gynecologist independent of the gatekeeper’s referral. It is my impression that this sustains the time-honored preference and practice of many women of continuing to depend on their gynecologist for well care. We must be prepared for this challenge.
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