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To investigate whether diet has a role in the development and progression of colorectal cancer (CRC).
MEDLINE was searched from January 1966 to December 2006 for articles on the relationship between diet and CRC using the key words colorectal cancer and folic acid, calcium, vitamin D, red meat, or fibre. Evidence that these factors are associated with CRC came from case-control and prospective cohort studies and some clinical trials.
Whether red meat is a culprit in causing CRC remains unanswered, although any effect it might have is likely moderate and related to processing or cooking. The effect of dietary fibre on risk of CRC has also been difficult to determine because fibre intake is generally low. Evidence that folic acid, calcium, and vitamin D reduce risk of CRC is stronger. In particular, recent research indicates that calcium and vitamin D might act together, rather than separately, to reduce the risk of colorectal adenomas. There might also be an interaction between low folate levels and high alcohol consumption and CRC.
Before dispensing dietary advice, physicians should understand the potential benefits and harm of specific components of various foods. People might be able to reduce their risk of CRC by increasing their vitamin and mineral levels through eating more vegetables and fruit. Multivitamin and mineral supplements can complement a healthy diet.
Déterminer si l’alimentation joue un rôle dans le développement et la progression du cancer colorectal (CCR).
On a recherché dans MEDLINE, entre janvier 1966 et décembre 2006, les articles sur la relation entre l’alimentation et le CCR à l’aide des rubriques colorectal cancer and folic acid, calcium, vitamine D, red meat ou fibre. Les preuves indiquant que ces facteurs influencent le CCR provenaient d’études cas-témoin et d’études de cohorte prospectives et de quelques essais cliniques.
La question de savoir si la viande rouge est un facteur dans le développement du CCR demeure sans réponse, quoique l’effet éventuel de ce facteur semble tout au plus modéré et lié au mode de cuisson. L’effet des fibres alimentaires sur le risque de CCR a aussi été difficile à évaluer parce que la consommation de fibres est généralement faible. Les preuves indiquant que l’acide folique, le calcium et la vitamine D réduisent le risque de CCR sont plus solides. Ainsi, les recherches récentes suggèrent que le calcium et la vitamine D agissent en synergie plutôt que séparément pour diminuer ce risque. Une interaction entre de bas niveaux de folates et une consommation élevée d’alcool pourrait aussi favoriser le CCR.
Avant de prodiguer des conseils d’ordre alimentaire, le médecin devrait être au fait des effets bénéfiques et nocifs des composantes spécifiques de différents aliments. Il est possible qu’on puisse réduire le risque de CCR si on augmente les niveaux des vitamines et des minéraux en consommant plus de fruits et de légumes. Des suppléments de multivitamines et de minéraux peuvent constituer un complément utile à un régime sain.
In Canada, colorectal cancer (CRC) is the second leading cause of death due to cancer among men and the third leading cause of death due to cancer among women. In 2004, about 11 900 men and 8800 women would have been diagnosed as new cases of CRC.1 Diet has long been thought to have a role in the etiology of CRC, particularly when a poor diet is combined with excess calorie intake and weight gain, physical inactivity, and unhealthy practices, such as smoking and consuming a great deal of alcohol.2–4
Current knowledge about food consumption patterns indicates that a diet high in vegetables, fruit, and fibre is protective against certain types of cancer, but the evidence that fruit and vegetable consumption is specifically related to a reduced risk of CRC was recently challenged.5 In an attempt to clarify the relationship between diet and CRC, researchers are examining individual dietary components, such as red meat, fibre, folic acid, calcium, and vitamin D. Some studies have focused on adenomas, precursors to CRC, or analysis of colon and rectal cancer, both separately and together.
MEDLINE was searched from January 1966 to December 2006 for articles on the relationship between diet and CRC using the key words colorectal cancer and folic acid, calcium, vitamin D, red meat, or fibre. These key words were chosen because they highlight controversies or are important focuses of current CRC and micronutrient research. More than 700 articles were identified, including many experimental studies. Evidence from case-control and prospective cohort studies (level II evidence) and clinical trials (level I evidence) is discussed below.
Consumption of red meat might be related directly to the incidence of CRC or indirectly because a diet high in meat tends to be low in vegetables, fruit, and fibre. Whether red meat itself or the method by which it is prepared influences risk of CRC has also been investigated.
Bidoli et al6 found that high intake of refined starches, eggs, cheese, and red meat increased risk of CRC. Risk of colon or rectal cancer was about twice as great among those who consumed these foods more frequently. On the other hand, more frequent consumption of tomatoes was associated with a 50% and 60% reduction in risk of colon cancer and rectal cancer, respectively.6 A study of CRC among people residing in northern Italy7 revealed that 17% of CRC cases were attributable to consumption of red meat.
The carcinogenic effect of heterocyclic amines, produced during cooking of red meat, has been suggested as the link between red meat and CRC. Probst-Hensch and colleagues8 found a more than twofold difference in the occurrence of distal colorectal adenomas among subjects who ate fried, darkly browned red meat more than once a week and subjects who ate red meat less often and ate it with a lightly browned surface. Sinha et al9 also found that well-done, grilled red meat was the main contributor to increased risk of cancer.
The relationship between consumption of meat and risk of CRC has been the focus of 2 meta-analyses. Sandhu et al10 determined that an increase of 100 g in daily consumption of all meat or red meat was associated with a 12% to 17% increase in risk of CRC. The authors noted, however, that the association might be confounded by other factors because only a few of the studies attempted to examine the independent effect of consumption of meat on risk of CRC. The second meta-analysis11 found that total meat consumption was not significantly associated with risk of CRC, but that consumption of red meat and processed meat was associated with about a 33% greater risk of CRC. This finding is supported by evidence from Argentina,12 where diets are rich in beef (almost 300 g daily for men). The number of deaths due to CRC among men in Argentina is comparable to that in Canada, but higher than that in other countries in Latin America.13
Whether consumption of red meat influences risk of CRC remains unclear (Table 16–12,14). A recent prospective cohort study by the National Cancer Institute14 showed no association between consumption of red meat, processed meat, or well-done meat and risk of CRC; however, the authors did not rule out the possibility of a modest association. Le Marchand15 noted that, in genetically predisposed people, consuming very well-cooked meat or meat cooked in direct contact with flames raises the risk of CRC.
Dietary fibre varies considerably in its physical properties and chemical composition, but can be classified according to its water solubility. This affects its action in the body and might be relevant to the issue of risk of CRC. Bran fibre is insoluble; fruit and vegetable fibre tends to be more soluble.
Terry et al16 examined fruit, vegetable, and fibre intake and risk of CRC among Swedish women known for their low consumption of fruit and vegetables and their high consumption of cereals. High consumption of fruit was associated with a 32% reduction in risk of CRC, while high intake of cereal fibre did not lower risk of CRC.
Asano and McLeod17 conducted a meta-analysis of 5 randomized controlled trials with subjects who had had adenomatous polyps removed, but who had no history of CRC. Dietary fibre interventions included wheat bran fibre, ispaghula husk, or high-fibre whole food alone or in combination. There was no difference between intervention and control groups with respect to the incidence or recurrence of adenomatous polyps over a 2- to 4-year period.
Whether dietary fibre has a direct or indirect effect on CRC is currently unknown (Table 216–21). Some researchers have suggested that a diet high in fat and meat and low in dietary fibre might affect the integrity of colonic cells.22 Others have suggested that certain plant cell-wall constituents, suberin and lignin, adsorb heterocyclic amines and thus protect against CRC.23 Potato skins contain suberin. Wheat bran contains lignin.
Levi et al18 found a significant inverse relationship between total fibre intake and risk of CRC (odds ratio 0.57, 95% confidence interval 0.47–0.68) and between certain types of fibre and CRC among 286 patients with CRC (149 with colon cancer and 137 with rectal cancer) compared with 550 controls. Vegetable fibre appeared to be more protective than either fruit or grain fibre.
In a large prospective cohort study in Europe,19 high intake of dietary fibre was inversely related to large-bowel cancer, but no food source of fibre was found to be more protective than any other. The researchers suggested that doubling dietary fibre intake among people with low average intake of dietary fibre could reduce the risk of CRC by 40%.
Fibre intake is generally low. The adequate intake for women 50 years old and older has been established at 21 g daily.24 In 1 study of older women,20 no association between fibre intake and CRC was observed, but in that study, the 10th percentile of dietary fibre intake was 5.4 g, and the 90th percentile was only 18.2 g. High intake of dietary fibre, however, was associated with a 27% lower risk of adenomas among subjects in 1 cancer screening trial.21
The observation that folic acid supplementation was associated with a substantial decrease in colon cancer among ulcerative colitis patients led researchers to examine the role of folic acid in prevention of CRC25 (Table 326–33). Two case-control studies in Majorca and Italy found a protective effect of folic acid on risk of CRC26,27. Bird and colleagues28 investigated folate and risk of adenomatous polyps; the strongest relationship was found between red-cell folate concentration and colorectal polyp development in men.
As is the case with breast cancer, an interaction between folate and alcohol might have a role in CRC. Kato et al29 found that women with low serum folate levels and high alcohol intake had a tendency toward greater risk of CRC. Giovannucci and colleagues30 determined that high intake of dietary folate was inversely associated with risk of colorectal adenomas. Also, women who drank more than 2 alcoholic drinks per day had an elevated risk of adenomas.
In the Nurses’ Health Study, Giovannucci et al31 found a considerably lower risk of colon cancer among women reporting use of multivitamins containing 400 μg of folate for 15 or more years. In practical terms, long-term folate supplementation reduced the number of new cases of colon cancer from 68 to 15 per 10 000 women aged 55 to 69. At least 1 other study32 has confirmed that having taken multivitamins containing folic acid in the past is associated with a reduced risk of CRC.
Platz et al33 suggested that modifying 6 risk factors (obesity, physical inactivity, alcohol consumption, smoking, red meat consumption, and low folic acid intake) could substantially reduce the incidence of colon cancer. Other studies34–39 have confirmed that modifiable risk factors, such as intake of dietary folate, alcohol consumption, and smoking, are important in cancer control.
Calcium and vitamin D are thought to reduce risk of CRC through mechanisms that decrease cell proliferation or promote cell differentiation.40 In general, cohort studies have found that milk and dairy products have a protective effect on CRC, but case-control studies do not support this relationship.41 Nevertheless, scientists are intrigued that the risk of dying from CRC is highest in geographic areas that get less sunlight.42 In contrast, the diet of people living in the Faroe Islands in the north Atlantic is high in fat and low in vegetables, but also high in fish, calcium, and vitamin D. Incidence rates of both colon and rectal cancer there were among the lowest in northwestern Europe and North America.43
Case-control studies have had inconsistent results (Table 443–62). In 2 studies of women,44,45 calcium intake was associated with reduced risk of CRC, but in a study involving both men and women,46 no significant association was observed for either calcium or vitamin D. In a Swedish study,47 increasing levels of vitamin D were inversely related to risk of rectal cancer or colon cancer, but the effect of calcium could not be documented. In 2 other case-control studies, calcium was found to be protective48 and not protective.49 In the first study, however, the patients all had confirmed adenocarcinomas, while in the second study, the patients were at different stages along the adenoma-carcinoma path.
Observations made in cohort studies have been conflicting. Three studies50–52 demonstrated that calcium had at least a modest effect on CRC risk reduction. Two studies53,54 showed no association between calcium and CRC risk. One study55 showed that high consumption of milk might reduce risk of colon cancer, but not because of its calcium or vitamin D content. Only the study by McCullough and colleagues50 showed an association between vitamin D and reduced risk of CRC, and then only in men.
In the New York University Women’s Health Study, an inverse association was found between fish and shell-fish consumption and CRC and between consumption of dairy products and risk of CRC.56
Epithelial cell proliferation was not altered by administration of calcium in 3 studies,57–59 but subjects in these trials were at high risk of cancer, had adenomas, or had had surgical treatment for CRC. For any specific micronutrient, the protective effect might be identified only after long-term high intake, either through diet or supplements or both. A 3-year intervention with calcium and antioxidants had no overall effect on polyp growth, but the authors suggested that calcium and antioxidants might have a protective effect against formation of new adenomas.60
Recent research indicates that calcium and vitamin D might act together, rather than separately, to reduce risk of colorectal adenomas.62 In a previous study,61 1200 mg of elemental calcium was associated with a moderate but significant reduction in risk of recurrent colorectal adenomas (P = .03). Grau et al62 found later that calcium supplementation was not associated with adenoma recurrence when vitamin D levels were at or below the median (29.1 ng/mL), and that vitamin D levels were associated with reduced risk only among those receiving calcium supplements.
Evidence that diet has an effect on the incidence of CRC is only moderate and might be affected by the multifactorial nature of CRC. Making appropriate choices across food groups, particularly with respect to fruit, vegetables, and fibre, is the key to healthy eating.
Patients could be advised to eat more vegetables and fruit for their folic acid and fibre content. Some patients at risk of CRC might benefit from a 400-μg folic acid supplement because of its higher bioavailability.
Patients could be advised to eat fish more often because it might provide some protection against CRC. Calcium and vitamin D might act together to reduce CRC risk; milk and canned salmon with bones provide both calcium and vitamin D. Dairy products such as yogurt and cheese provide calcium only; canned light tuna provides vitamin D. Supplementation with calcium and vitamin D might benefit some patients.
Evidence derived from properly conducted randomized, double-blind controlled clinical trials
Evidence originating from well-designed controlled clinical trials or well-designed multicentre, prospective cohort, or case-control epidemiologic studies
Evidence obtained from respected authorities with clinical experience, descriptive studies, or reports of expert committees, such as reports from consensus conferences
This article has been peer reviewed.
Dr Ryan-Harshman received a grant from Wyeth Consumer Healthcare Inc to co-author this article, and Dr Aldoori is an employee of Wyeth Consumer Healthcare Inc.