Energy intake, body mass index, physical activity, and the colorectal adenoma-carcinoma sequence.

Little is known about the precise relationship between energy intake, overweight, sedentary lifestyle, and steps in the colorectal adenoma-carcinoma pathway. We studied these parameters within a case-control study. Patients with adenomas < 10 mm (n = 154) or > 10 mm (n = 208) were compared with polyp-free controls (n = 426) for determining factors associated with adenoma formation, i.e., observed for small and large adenomas, or with adenoma growth only. Colorectal cancer cases (n = 171) were compared with population controls (n = 309) to determine factors specific to the final stage, cancer. Exercise reduced the risk of cancer [odds ratio (OR) = 0.3, 95% confidence interval (CI) = 0.2-0.5 for high vs. low physical activity] but had little influence on adenomas. High energy intake increased the risk of cancer [OR for 5th vs. 1st quintile (OR5) = 1.6, 95% CI = 0.9-2.9, p = 0.02], but not of adenomas. High body mass index (BMI) significantly increased the risk of large adenomas (OR5 = 2.1, 95% CI = 1.2-3.5, p = 0.02 and OR5 = 1.7, 95% CI = 1.0-3.1, p = 0.25) for large and small adenomas vs. polyp-free controls. Neither height nor weight nor BMI influenced the risk of cancer. Results were unmodified when controlling for dietary risk factors and family history. Energy intake, a sedentary lifestyle, and high BMI were independently associated with a high risk of cancer itself or large adenomas, which indicates an effect on promotion of colorectal tumors. These findings suggest that preventive advice regarding these factors should be provided, even late in life, to decrease the risk of colorectal cancer.

Foods as risk factors for colorectal cancer: a case-control study in Burgundy (France).

Although the high meat-low vegetable diet is considered the reference high-risk diet for colorectal cancer, particularly in USA communities, other at-risk dietary patterns, such as high intakes of processed meat and refined carbohydrates are emerging. Little is known about risk factors for colorectal cancer in France, a country at high risk of rectal cancer and moderately high risk of colon cancer. We compared diet of colorectal cancer cases (n = 171) and general population controls (n = 309) in Burgundy (France). Categories of intake were established by sex and based on the distributions of food intakes in controls. Odds ratios for the fourth vs first quartile of intake (OR4) were 2.0 (1.1-3.6) for refined cereal products (rice, pasta and pastry), 2.4 (1.3-4.5) for delicatessen, 2.3 (1.2-4.2) for patés, 1.7 (1.1-2.8) for offal and 2.1 (1.1-4.0) for butter, lard and cream. There was no association with consumption of fresh meat (OR4 = 1.2), fish (OR4 = 1.5), egg (OR4 = 1.1) or dairy products (OR4 = 1.0). A protective effect of vegetables was only observed for left colon cancer (OR3 = 0.3; 0.1-0.6). In men, the most significant risk factors were refined cereal products, seasoning animal fats, chocolate and coffee, whereas risk factors were delicatessen, fat meat, pasta, rice, and chocolate in women. The strong association with refined cereal products is consistent with the hypothesis of a role of hyperinsulinism in colorectal carcinogenesis. The association with processed but not fresh meat suggests the importance of exogenous carcinogenesis in that area.

Folate and alcohol intakes: related or independent roles in the adenoma-carcinoma sequence?

Epidemiologic studies have suggested that high alcohol and low folate intakes might be jointly associated with colorectal tumors via DNA metabolism. We investigated this hypothesis in a case-control study comparing small adenoma (< 10 mm, n = 154), large adenoma (n = 208), and polyp-free (n = 426) subjects, recruited after colonoscopy, and cancer cases (n = 171) with population controls (n = 309). Odds ratios for the fifth vs. the first quintile of intake (OR5) were as follows: Folate intake was related to the risk of small and large adenomas compared with polyp-free subjects [OR5 = 0.5, 95% confidence interval (CI) 0.3-1.0; OR5 = 0.5, 95% CI 0.3-1.0, respectively], whereas alcohol was related to risk of large adenomas (OR5 = 4.1, 95% CI 2.1-8.1), but not of small adenomas (OR5 = 1.2, 95% CI 0.7-2.2). In large adenomas, there was some interaction between alcohol and folate, with a stronger protective effect of folate with high alcohol intake and a stronger risk with alcohol with low folate intake. For cancer patients compared with general population controls, neither alcohol (OR5 = 1.6, 95% CI 0.8-3.0) nor folates (OR5 = 1.0, 95% CI 0.5-2.0) were related to risk. Our data support the hypothesis that folate intake might be mostly beneficial to prevent adenoma formation but might have an additional protective effect against adenoma growth associated with alcohol.

Intervention trials on colorectal cancer prevention.

Epidemiological studies have emphasized the major role played by diet in the etiology of large-bowel cancer. Attempts to identify causative or protective factors in epidemiological and experimental studies have led to some discrepancies. The time has come to test the most important hypotheses within the framework of intervention studies. Of 14 studies specifically devoted to colorectal carcinogenesis, nine have been completed and five are ongoing; all the studies evaluate the effect of the intervention on adenoma recurrence and three studies also examine adenoma growth. In addition, five intervention trials considering cardiovascular diseases and various cancer sites will provide data on the effect of the intervention on colorectal cancer incidence. The interventions being evaluated are supplements of vitamins (with or without other antioxidants), fibre or calcium, as well as dietary modifications. Most available data do not support a protective effect of vitamins and antioxidants on colorectal carcinogenesis. There are some arguments in favour of a protective effect of dietary fibre and/or a low-fat diet on adenoma growth. The results of ongoing studies will be available within two to three years. If one of the evaluated interventions proves effective, it will indicate a simple, safe and inexpensive prophylaxis for a very common cancer.

[Primary prevention of colorectal cancer]. / Prévention primaire du cancer colorectal.

Results from case-control studies and prospective studies suggest that diet is involved in the causation of large bowel cancer either as initiator, promoter or inhibitor of carcinogenesis. Available data are not sufficient to serve as a basis for firm specific dietary advice. In the present situation it is attractive to investigate available hypotheses within the frame work of intervention trials. The adenoma appears to be one of the most appropriate end point of intervention studies. Several arguments indicate that the adenoma-carcinoma sequence is a multistep process. Colorectal cancer could possibly be prevented by intervening in the development of a small adenoma or in the growth into a large adenoma. Four intervention trials have been published so far. One of them suggest a protective effect of antioxidants vitamins on adenoma recurrence and three of them conclude to the absence of effect of these vitamins. A protective effect of lactulose on adenoma recurrence has also been suggested. Three studies are currently evaluating the effect of calcium supplementation on adenoma recurrence or growth of calcium supplementation, three studies the effect of fibre supplements, two studies the effect of antioxidants (one of them with calcium) and two studies the effect of diet intervention. The results of these studies will be available within three years.