indicating changing cancer rates in mi- ... be an increase in secretion of bile acid ... 1989 (%). Men. Lung. Prostate. Colorectum. Bladder. Stomach. (18). (15). (14). (7). (7) .... during reflux, aiding in the neutralization of refluxed gastric acids.
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Gregory Hislop, MD
Diet and Cancer SUMMARY
RESUME
Most of the common cancers in Canada have Au Canada, la plupart des formes courantes de cancer ont ete associees d'une facon ou d'une autre a been associated in some way with diet. l'alimentation. Pour chacun des sexes, plus de la More than half of all newly diagnosed moitie de toutes les tumeurs nouvellement cancers and cancer-related deaths are diagnostiquees et de tous les deces attribuables au limited to three sites in each sex: lung, cancer sont limites a trois sites: poumon, prostate, prostate, and colorectum in men and breast, colorectum chez les hommes, et sein, colorectum et poumon chez les femmes. Les preuves colorectum, and lung in women. The epidemiologiques les plus recentes et les plus earliest and strongest epidemiologic associant alimentation et cancer nous plausibles evidence associating diet and cancer has proviennent d' etudes descriptives de correlation. Les come from descriptive correlation studies. trouvailles des etudes analytiques subsequentes et The findings of subsequent, more powerful, plus puissantes s'averent inconsistantes. L'auteur analytic studies have been inconsistent. The passe en revue l'importance de l'alimentation dans les formes courantes de cancer au Canada et examine author reviews the importance of diet for les limitations methodologiques des protocoles common cancers in Canada and considers d'etude. the methodologic limitations of various study designs. (Can Fam Physician 1990; 36:973-975.) Key words: diet, family medicine, oncology, risk factors Dr. Hislop is Senior Epidemiologist at the Division of Epidemiology, Biometry and Occupational Oncology, Cancer Control Agency of British Columbia, Vancouver. Requests for reprints to: T. Gregory Hislop, Cancer Control Agency of British Columbia, 600 West 10th Ave., Vancouver, B.C. V5Z 4E6 T HERE WERE several major reviews in the early 1980s about the relationship between diet and cancer. In 1981, Doll and Peto estimated that diet might contribute to 10% to 70% of all cancer deaths in the United States.' In 1982, the National Research Council Committee on Diet, Nutrition and Cancer reviewed the literature and published "interim dietary guidelines" to reduce the likelihood of cancer.2 The two major sources of evidence that were reviewed came from epidemiologic studies and laboratory animal studies. Laboratory studies are useful for examining biological mechanisms; they are, however, limited in their application to human cancers. CAN. FAM. PHYSICIAN Vol. 36: MAY 1990
The earliest and strongest epidemiologic evidence associating diet and cancer has come from descriptive studies correlating cancer incidence and mortality rates with per capita consumption of specific foods among different populations and from migrant studies indicating changing cancer rates in migrants toward those of the adopted country. Subsequent, more powerful, analytic epidemiologic studies have been inconsistent in their findings.3'8 This paper reviews the importance of diet for the common cancers in Canada.
Cancer in Canada There were estimated to be more than 100 000 newly diagnosed cancer cases and more than 50 000 cancer-related deaths in Canada during 1989.9 Table 19-ll lists the leading cancer sites, excluding non-melanoma skin cancer, in Canadian men and women during the last two decades. More than 50% of all newly diagnosed cancers and cancer-related deaths in 1989 were limited to three sites in each sex: lung, prostate, and colorectum in men and breast, colorectum, and lung in women. The most
notable temporal change has been the increase in lung cancer in women. Although lung cancer is largely attributed to smoking, recent studies have shown an additional independent increase in risk of lung cancer in persons with low carotene intake. Most of the other common cancers in Canada are also associated with diet.
Associations of Diet with Cancer Dietary Fat Dietary fat has been associated with cancers of various sites, including breast, colorectum, prostate, ovary, and endometrium. The evidence from analytic studies is strongest for colon cancer. One mechanism is postulated to be an increase in secretion of bile acid and alteration of colonic bacteria that results in the formation of secondary bile acids (possible promoters of colon cancer). The evidence is less consistent for breast cancer, with some support from case-control studies but little from cohort studies. The current epidemiologic literature suggests that dietary fat levels 973
need to be below 30% of total energy, or possibly reduced at early ages, in order to influence breast cancer rates; international comparison studies suggest a fourfold risk reduction with 60% reduction in total fat.6 Few studies have examined the effect of dietary fat for the other cancer sites.
otene, have been suggested to prevent or reverse the progression to malignancy for various sites, including lung, larynx, colorectum, prostate, bladder, stomach, and esophagus. The evidence comes
from both laboratory and epidemiologic studies; however, it is not yet conclusive. Vitamin C is known to block the forDietary Fibre mation of nitrosamines and other N-niA protective effect of dietary fibre for troso compounds from nitrates and nicolorectal cancer has been proposed for trites. (Nitrates and nitrites, used as prea number of years; this suggestion origi- servatives in cured foods and also found nated from observations of high fibre in- in many vegetables, have been linked to take and disease patterns in certain Afri- stomach cancer.) Several epidemiologic can populations. Fibre has been postu- studies have associated low consumplated to act by binding carcinogens and tion of fruits and vegetables with canpromoters (such as bile acids), by alter- cers of the stomach and esophagus; ing colonic bacteria, and by reducing these food sources contain vitamin C to exposure to harmful substances in fecal varying extents. As yet, the evidence is material (by shortening bowel transit inconclusive. time and increasing fecal bulk). Vitamin E also hinders the formation Descriptive studies have shown cor- of nitrosamines. There is no epidemiorelations with fibre-containing foods logic evidence supporting a protective and colon cancer in different popula- effect, however, because this vitamin is tions. The protective effect of fibre or widely distributed in many foods and fibre-containing foods, however, is not hence is difficult to study. yet established. It is becoming apparent The mineral selenium has been that "dietary fibre" is a general term proposed to reduce cancer risk by detoxcovering a number of different and dis- ification and inhibition of damage from tinct substances; any beneficial effect free radicals. As with vitamin E, this could be limited to specific types of mineral is difficult to investigate befibre. cause it is widely and inconsistently distributed in many foods. Micronutrients The evidence for protective effects Several micronutrients have been with micronutrients has come largely suggested to have protective effects for from laboratory animal studies. The certain cancers; these include the vita- epidemiologic evidence to date is inconmins A, C, and E and the mineral sele- clusive. Chemoprevention trials curnium. Vitamin A and its precursor, car- rently under way for some micronutri-
Table 1 Relative Frequency for Leading Sites of New Cancer Cases and Cancer-Related Deaths in Canada During 1970 and 1989 New Cancer Casesa Cancer-Related Deathsa 1970 (%) 1989 (%) 1970 (%) 1989 (%) Men (18) Lung (22) Lung (25) Lung (33) Lung Prostate (17) Colorectum (14) Prostate (11) (15) Prostate Colorectum (14) Colorectum (14) Stomach (1 0) Colorectum (10) Bladder (7) Bladder (7) Prostate (10) Lymphoma (5) Stomach (7) Lymphoma (6) Pancreas (6) Pancreas (5) Women Breast (20) (29) Breast (26) Breast (21) Breast Colorectum (1 6) Colorectum (15) Colorectum (18) Lung (17) Endometrium (7) Lung (11) Stomach (7) Colorectum (12) Cervix uteri (7) Endometrium (6) Ovary (7) Pancreas (5) Ovary (5) Lymphoma (6) Lung (6) Lymphoma (5) a. Excluding non-melanoma skin cancer. Source: See references 9-11 . 974
ents are expected to clarify their effectiveness in reducing cancer incidence; these trials are summarized elsewhere.'2
Salt Descriptive studies have correlated stomach cancer with high intake of salted or nitrite-cured foods, especially in populations with low intake of fruits and vegetables. Stomach cancer is now relatively uncommon in Canada. The decrease in stomach cancer has been largely attributed to the introduction of refrigeration and subsequent reduction in consumption of preserved foods. Alcohol Alcohol consumption has been reported in epidemiologic studies to act synergistically with smoking to increase the risk of oral, laryngeal, esophageal, respiratory, and hepatic cancers. Recent studies have also associated moderate alcohol intake with breast cancer; the effect might be limited, however, to consumption before age 30.7 This association needs further investigation. Food Additives and Contaminants There is no evidence to date that food additives, contaminants (such as aflatoxin), and products of cooking contribute significantly to cancer in Canada.
Energy Balance There is growing interest in the complex relationships between caloric intake, energy expenditure, body weight, and cancer risk. Animal studies have shown that severe diet restriction reduces the incidence of both spontaneous and induced cancers. Epidemiologic studies of colon and breast cancers, however, have been less consistent. Breast cancer has been directly associated with obesity in postmenopausal women, and there is recent evidence for a reversed effect in premenopausal women. In addition, a direct association with body height and breast cancer risk has been reported in populations with food shortages restricting dietary intake before age 20. There is less evidence for an obesity relationship in colon cancer; an effect has been reported only in men. Endometrial cancer is strongly a,sociated with obesity, probably through the production of estrogens by adipose tissue. There is some evidence for an association of obesity and prostate cancer. A protective effect for exercise has been found in several epidemiologic studies of colon and breast cancer. CAN. FAM. PHYSICIAN Vol. 36: MAY 1990
Methodologic Limitations The methodologic limitations of laboratory and epidemiologic studies have been reviewed elsewhere.3 4 68 The most consistent epidemiologic evidence has come from descriptive studies, which have the weakest design. Analytic epidemiologic studies have generally reported inconsistent findings. These studies are more powerful than descriptive studies; however, they are subject to the limitations of relatively homogeneous diets in the study groups and dietary measurement error. Case-control studies are subject to bias in dietary recall, and differences in accuracy of recall between cases and controls could invalidate the findings of a study. Cohort studies have generally given the least support for a relationship between diet and cancer; however, they are often limited to examining short-term dietary effects using short self-administered dietary assessment instruments. The methodologic design of dietary studies has improved recently. Methods for sampling the study groups (especially controls), dietary assessment instruments, and data analysis have improved for case-control studies. Cohort studies are becoming more common. It might not be possible, however, to measure specific dietary nutrients reliably by the methods required for analytic epidemiologic studies. Randomized clinical trials, the most powerful design, could be needed to demonstrate the importance of these dietary factors clearly. Several such trials are currently under way in chemoprevention and dietary in-
tervention.'2
Dietary Recommendations We still need more definitive answers about the relationship between diet and cancer. Despite the absence of conclusive evidence, interim guidelines have been formulated that are nutritionally sound, are consistent with other recommendations for cardiovascular disease, and could reduce the likelihood of certain types of cancer. The current guidelines of the Canadian Cancer Society are as follows. 1. Reduce total fat intake. 2. Eat more fibre-containing foods. 3. Have several servings of vegetables and fruit every day. 4. Keep weight close to the ideal. 5. If consuming alcohol, have two or fewer drinks. CAN. FAM. PHYSICIAN Vol. 36: MAY 1990
6. Minimize the consumption of smoked, nitrite-cured, and salted foods. '3 It is food choices, rather than the use of specific supplements, that should be considered because it is not yet clear which particular nutrients are important. We await more definitive answers from more rigorous studies, including chemoprevention and diet intervention trials. a
Acknowledgements I thank G. Pomeroy for assistance in preparing the manuscript.
References 1. Doll R, Peto R. The causes of cancer. Oxford: Oxford University Press, 1981. 2. Committee on Diet, Nutrition and Cancer, Assembly of Life Sciences, National Research Council. Diet, nutrition and cancer. Washington, DC: National Academy Press, 1982:14-6.
3. Hislop TG, Band PR. Epidemiology of diet and cancer. BC MedJ 1987; 29:675-80. 4. Bright-See E. Diet and prevention of cancer: the state of knowledge and current dietary recommendations. JCan DietAssoc 1987; 48:13-20.
5. Byers T. Diet and cancer. Any progress in the interim? Cancer 1988; 62:1713-24. 6. Prentice RL, Pepe M, Self SG. Dietary fat and breast cancer: a quantitative assessment of the epidemiological literature and a discussion of methodological issues. Cancer Res 1989; 49:3147-56.
7. Willett W. The search for the causes of breast and colon cancer. Natur-e 1989; 338:389-94. 8. Goodwin PJ, Boyd NF. Critical appraisal of the evidence that dietary fat intake is related to breast cancer risk in humans. JNatl Cancer Inst 1987; 79:473-85.
9. National Cancer Institute of Canada. Canadian cancer statistics 1989. Toronto: National Cancer Institute of Canada, 1989. 10. Statistics Canada. New primary sites of malignant neoplasms in Canada. 1970. Ottawa, Ont.: Statistics Canada, 1972; catalogue no. 82-207. 11. Statistics Canada. Canada causes of death: provinces by sex and Canada by sex and age. 1970. Ottawa, Ont.: Statistics Canada, 1971; catalogue no. 84-203. 12. Bright-See E. Diet and cancer prevention: separating fact from myth. Can Fam Physician 1985; 31:1293-6.
PRESCRIBING
INFORMATION COMPOSITION: Each 5 mL (1 tsp) of GAVISCON liquid contains sodium alginate, 250 mg; aluminum hydroxide, 100 mg. Each GAVISCON tablet contains alginic acid, 200 mg; aluminum hydroxide dried gel 80 mg; and as non-medicinal ingredient magnesium trisilicate. INDICATIONS: For symptomatic treatment of heartburn and oesophagitis associated with gastric acid reflux. This often accompanies ineffective lower oesophageal sphincter tone as in hiatus hernia, or pregnancy and nasogastric intubation. DOSAGE: Adults: 10 to 20 mL (2 to 4 tsp) of GAVISCON Liquid, or 2 to 4 GAVISCON tablets, 1 to 4 times daily, after meals and on retiring. ACTION: GAVISCON liquid or GAVISCON tablets, when chewed, produce a viscous, demulcent antacid foam which floats on the stomach contents serving as a protective barrier for the oesophagus against reflux of gastric contents. The alkaline foam readily flows into the oesophagus during reflux, aiding in the neutralization of refluxed gastric acids. GAVISCON also effectively reduces the frequency of reflux episodes. ADMINISTRATION: GAVISCON liquid may be followed by a sip of water, if desired. GAVISCON tablets must be chewed thoroughly, and may be followed by a drink of water or milk if desired. CONTRAINDICATIONS: There are no specific contraindications for GAVISCON LIQUID and GAVISCON FOAMTABS. See "Precautions" below. PRECAUTIONS: Each 5 mL of GAVISCON liquid contains approximately 30 mg and each GAVISCON tablet contains approximately 22 mg of Na+ which should be noted for patients on severely restricted sodium diets. The divalent cations of magnesium and aluminum interfere with the absorption of tetracycline, iron and phosphate. In addition, oral magnesium may accumulate in the plasma of patients with impaired renal function. Each 5 mL of GAVISCON liquid contains 20 mg of sodium cyclamate, an artificial sweetener. Each GAVISCON tablet contains 1.2 g of sucrose which is equivalent to 4.7 calories. ADVERSE EFFECTS: Nausea, vomiting, eructation, flatulence. OVERDOSAGE: Should overdosage occur, gastric distention may result and is best treated conservatively. PRESENTATION: GAVISCON LIQUID is a light tan-coloured, pleasantly flavoured suspension supplied in plastic bottles of 340 mL. GAVISCON FOAMTABS are round creamy-white butterscotch or fruit flavoured tablets with the name "GAVISCON" imprinted on one side and the lefter "W" imprinted on the opposite side. Supplied in plastic boftles of 100 tablets and boxes of 10 and 50 blister packaged tablets. STORAGE PRECAUTIONS: GAVISCON liquid should be stored in a cool place. GAVISCON tablets should be stored in a dry place. Product Monograph available upon request.
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Division of Sterling Drug Ltd* Aurora, Ontario L4G 3H6 User -Registered Reg. Trade Mark PAAB
13. Canadian Cancer Society. Facts on
cancer and diet. Toronto: Canadian Cancer Society, 1986. 975
