In the name of God

EPIDEMIOLOGY OF COLORECTAL CANCER Mohsen Janghorbani Professor of Epidemiology Isfahan University of Medical Sciences

INTRODUCTION 98% adenocarcinoma. 1 / 2 CRC in rectum and rectosigmoid, 1 / 4 in sigmoid, 1 / 4 in caecum, ascending, transverse and descending colon. 3/4 of primary CRC will also have benign adenoma.

WORLWIDE INCIDENCE FOR CRC Incidence varies in different region of the world, increased in N. America, W. Europe, Australia, New Zealand. Higher incidence in industrialized areas, 8.5% of all new cancer cases diagnosed worldwide. Groups that move to high risk areas assume the risk of that geographical region.

DESCRIPTIVE EPIDEMIOLOGY Gender Age Ethnic/ race Socio-economic status

Geographical distribution High risk areas include North America, Europe and Australia. Low risk areas include Central and South America, Asia and Africa.

ESTMATED RATES OF CRC INCIDENCE BY GENDER AND AREA

SECULAR TRENDS The numbers of new cases of colorectal cancer worldwide has increased rapidly since 1975.

RISK FACTORS Genetic Environmental factors

GENETIC FACTORS Familial adenomatous polyposis. Hereditary non-polyposis CRC. History of CRC in first degree relatives Inflammatory bowel disease (Crohn and, specially, ulcerative colitis).

DIETARY AND NUTRITIONAL PRACTICE Energy intake Meal frequency Adult height High body mass Physical activity Carbohydrates Extrinsic sugars

DIETARY AND NUTRITIONAL PRACTICE Fat and cholesterol Protein Alcohol Vitamins Minerals Foods and drinks

ENERGY INTAKE Total energy intake has no simple relationship with CRC risk, but its effect may be dependent on levels of obesity and physical activity. Whatever the reason, the data on energy intake and CRC are inconsistent; no judgment is possible.

MEAL FREQUENCY 5 case control studies have shown a small increase in risk (10 to 20%) associated with each daily eating occasion. Frequent eating possibly increases the risk of CRC.

ADULT HEIGHT 4 cohort studies have found an increase risk in association with greater stature and colon cancer. In contrast, case control studies have found no association between height and CRC. Being tall as an adult possibly increase the risk of CRC.

BODY MASS INDEX One cohort and 4 case-control studies were null. 3 cohort and 8 case-control studies found positive results. Obesity possibly increases risk of CRC, particularly in men, but perhaps not rectal cancer.

PHYSICAL ACTIVITY AND COLON CANCER Of 9 cohort study only 2 reported no substantial association. Of 11 case-control studies only 1 study reported increased risk. The evidence that physical activity, specially when life-long, decrease the risk of colon cancer, is convincing, but not for rectal cancer.

PHYSICAL ACTIVITY AND RECTAL CANCER 2 cohort study reported higher level of activity are associated with weak increase in risk of rectal cancer. Of 7 case control studies 4 reported no substantial association. The evidence relating to physical activity, and the risk of rectal cancer is more limited and inconsistent; no judgment is possible.

Carbohydrates Evidence on diet high in starch and the risk of CRC is rather inconsistent. Diet high in starch possibly decrease the risk of CRC.

EXTRINSIC SUGARS One cohort and 8 case-control studies have shown the diet comparatively high in refined sucrose are associated with increase risk of CRC. 4 further studies found no or weak association. Diet high in extrinsic (refined) sugars possibly increase risk of CRC. Evidence is strongest for sucrose.

FIBER Data from prospective study weakly supportive of fiber hypothesis. 2 meta analysis of 13 and 16 case control studies provided evidence for a linear reduction in CRC. Diets high in fibers possibly decrease the risk of CRC.

FAT Diet high in total fat or saturated fat possibly increase the risk of CRC. The evidence on mono- or polyunsaturated fat and CRC is inconsistent; no judgment is possible. This evidence is obtained from ecological studies, animal experiments, and case- control and cohort studies.

CHOLESTEROL 2 cohort studies found no association. One meta-analysis of 13 case control studies of CRC found a weak increase in risk. An ecological study reported a positive correlation between cholesterol and colon cancer mortality. In 9 of 11studies egg consumption was associated with the risk of colon cancer and with rectal cancer in 6 of 8 studies.

CHOLESTEROL The evidence suggests that dietary cholesterol may increase the risk of CRC but the overall picture is also consistent with no association, no judgment is possible.

PROTEIN 5 cohort studies and 8 of 15 case control studies found no association. The epidemiological evidence for an association of protein with CRC is inconsistent; no judgment is possible.

ALCOHOL High alcohol consumption probably increase the risk of CRC. The effect generally seems to be related to total ethanol intake irrespective of the type of drink.

VITAMINS High dietary carotenoid intake possibly decreases the risk of CRC. High dietary vitamin C, E, folate, and methionine intake may reduce the risk of CRC; but the evidence is, at present, insufficient.

MINERALS Evidence suggests that vitamin D may reduce the risk of CRC; but the evidence is, at present, insufficient. The evidence on calcium suggest that there may be a very week overall reduction in risk but the conservative judgment is that there is possibly no relationship.

MINERALS Dietary selenium is possibly unrelated to the risk of CRC. The evidence suggest that iron intake may increase the risk of CRC, but is, as yet, insufficient.

FOODS AND DRINK The evidence suggests that cereals may reduce the risk of CRC; but are currently insufficient. The evidence on roots and tubers including, especially potato, is inconsistent, no judgment is possible.

FOODS AND DRINKS Evidence that diets rich in vegetables protect against CRC is convincing. The data on fruit are more limited and inconsistent; no judgment is possible. The evidence relating to pulses and the risk of CRC, is inconsistent, no judgment is possible.

FOODS AND DRINKS The evidence relating to nuts and seeds and the risk of CRC is very limited, no judgment is possible. The evidence shows that red meat probably and processed meat possibly increases risk of CRC.

FOODS AND DRINKS The data on poultry consumption are inconsistent; it may be that poultry has no relationship with CRC, but no judgment is possible. Diet high in fish possibly have no relationship with the risk of CRC.

FOODS AND DRINKS Consumption of eggs possibly increases risk of CRC. The evidence on the relationship between CRC and dairy products is inconsistent, no judgment is possible. The evidence suggests that coffee may decrease the risk of CRC but is, as yet, insufficient.

FOODS AND DRINKS The data on the relationship between chlorinated drinking water and CRC are inconsistent; no judgment is possible. Cooking meat at high temperature possibly increases the risk of CRC.

HORMONE REPLACEMENT THERAPY Increasing evidence supports an association between hormone replacement therapy and a reduced risk of colorectal cancer. Of 19 published studies of hormonal replacement therapy and risk of colorectal cancer, 10 support an inverse association and a further five show a significant reduction in risk.

ASPIRIN AND NSAID A substantial body of evidence supports a protective effect of aspirin and other nonsteroidal antiinflammatory drugs on the development of colon cancer.

SMOKING Cigarette smoking is associated with an increased tendency to form adenomas and develop CRC.

CONCLUSION The evidence that diets high in vegetables and regular physical activity decrease the risk of CRC, is convincing. Alcohol, and consumption of diets high in red meat, probably increase the risk of CRC.

CONCLUSION Diets high in starch, non-starch polysaccharides (fiber) and carotinoids all of which possibly decrease risk of CRC. Obesity, adult height, frequent eating, and diet high in sugar, total and saturated fat, eggs, and processed meat, all possibly increase risk of CRC.

Established non-dietary causes of CRC include genetic predisposition, ulcerative colitis, infection with Schistosoma sinesis and smoking. Aspirin and NSAIDs decrease risk of CRC.

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