Our data are the first to describe relations between dietary patterns and colorectal tumors at the various stages of the adenoma-carcinoma pathway in a prospective study. In this large cohort of French women, we observed an increased risk of adenomas with high scores of the Western and drinker dietary patterns, while a protective effect of the healthy pattern was only suggested. High-risk adenomas were positively associated with only the Western pattern in older women. The meat eaters pattern was associated with an increased risk of colorectal cancer. The associations of patterns with risk were stronger in women over the age of 51 years (the median age in our population) than in younger women; this is consistent with the hypothesis that the genetic component of risk is stronger in younger women, while the part attributable to environmental factors such as diet is stronger in older women. It is noteworthy that our median age of 51 years was close to the 50-year median age at menopause; an effect modification by menopause cannot therefore be ruled out and should be explored in further larger-scale studies. Generalizability of the defined patterns may be discussed, as our cohort was based on volunteers who had a higher level of education than the general French population. However, patterns similar to some of ours were already described in previous studies (18
), adding to the consistency of our findings. An excessive homogeneity of our population is a potential limitation of our study, as it may be responsible for a lack of power for demonstrating relations between tumors and patterns, especially for the healthy pattern.
For this study, we had excluded all cases of prevalent tumors at baseline in order to produce patterns from the diet of cancer-free subjects. Recall bias was avoided by the prospective design of the E3N-EPIC study. The high educational level and strong involvement of the participants, as highlighted by a 85 percent response rate after 10 years of follow-up, accounted for the good quality and reproducibility of the dietary data (23
). Regarding the adenoma study, bias was limited by histologic confirmation of all cases and inclusion of polyp-free subjects as noncases, in order to avoid misclassification of noncases and to control for surveillance bias. Because adenomatous polyps are asymptomatic tumors, some of the adenoma subjects may have had their adenomas at the time of the dietary interview, resulting in some misclassification of the time at risk. An accurate classification of time at risk would be very difficult to achieve; it would require a baseline polyp-free colonoscopy in all cohort subjects and then regular follow-up colonoscopies. However, only major changes in the diet of a large proportion of adenoma subjects would hamper a study such as ours, which are unlikely to have occurred as subjects were unaware of their having a polyp. The 6.3-year follow-up in the cancer analysis and 3.3-year follow-up in the adenoma analysis were relatively short, resulting in a limited number of cases and reduced statistical power. However, because events in the adenoma-carcinoma sequence are separated by 3- to 5-year periods (27
), this short follow-up period may be an advantage in that exposure likely corresponds to the studied step of the adenoma-carcinoma sequence. Traditionally, associations between diet and diseases are investigated through the analysis of selected nutrients or foods. Recently, the more global approach of dietary pattern assessment has emerged, including “a posteriori” analyses such as cluster and factor analyses and “a priori” analyses based on dietary recommendations (12
). These studies classify people according to a global food consumption behavior, while the nutrient-food approach may be easier for interpretability and understanding of the mechanisms involved (29
). The identification of dietary patterns by factor analysis has some limitations (12
), in particular as it involves subjective decisions such as the choice and definition of the food groups included in the factor analysis step, the number of components to extract, and the labeling of the identified patterns (31
). In a recent review, Newby et al. (32
) demonstrated the stability over time of dietary patterns derived from factor analysis, as well as reproducibility across populations, especially regarding major patterns such as healthy and Western. In our study, we identified a typical Western pattern, as previously described (32
), that was associated with adenomas but also a pattern characterized mostly by high meat intake, thus sharing only part of the characteristics of a usual Western diet, which was associated mainly with colorectal cancer.
In a US case-control study (16
), a Western pattern characterized by a high consumption of processed meat, organ meats, red meat, fast-food meat, eggs, butter, margarine, high-fat dairy foods, coffee, canned fruit, nuts, legumes, potatoes, high-sugar drinks, and high-sugar desserts was associated with a high risk of colon cancer in women. A prudent pattern, correlated with fresh juice, legumes, cruciferous vegetables, salad, carrots/tomatoes, and other vegetables, was associated with decreased risk, in agreement with our findings. Similarly, in the Nurses’ Health Study (16
), a Western pattern was positively associated with the risk of colon cancer, while the protective effect of a prudent pattern was suggested. In a Swedish study (17
), there was a nonstatistically significant negative association between the risk of colorectal cancer and the healthy pattern. In the opposite, in a country-specific analysis of four European cohort studies (DIETSCAN) (14
), two common dietary patterns, i.e., vegetables and pork–processed meats–potatoes, were identified, but they were not consistently associated with colorectal cancer risk. Fewer studies have attempted to describe the relation between dietary patterns and colorectal adenomas. In a casecontrol study, a pattern defined by cluster analysis and characterized by a high consumption of bread, pork, oils other than olive oil, wine, starchy foods, and high-fat processed meat and a low consumption of fruit and vegetables was associated with an increased risk of both colorectal adenomas and cancers (18
). In an intervention study on adenoma recurrence, high scores of a pattern characterized by a high consumption of oil, vegetables, fruit, legumes, and poultry tended to be associated with a decreased risk of adenoma recurrence in the left colon (20
). Only one prospective study, in Japanese men, described associations between dietary patterns and colorectal adenomas. A significant inverse association was observed with a high-dairy, high-fruit and vegetables, high-starch, and low-alcohol pattern (19
). Our findings are consistent with the most commonly described relations between colorectal tumors and diet. Adenomas, the precursor lesions to most colorectal cancers, have been found to be associated with a diet low in folate and high in alcohol (34
), low in dietary fiber (36
), and low in fruit and vegetables (37
), in agreement with the observed association with the Western and drinker patterns. The positive association between the meat eaters pattern and risk of colorectal cancer can be explained by an effect of red meat and processed meat on colorectal carcinogenesis (4
). Mechanisms underlying such a relation involve their content in fat, heme iron, N-nitroso compounds, heterocyclic amines, and polycyclic aromatic hydrocarbons due to cooking at high temperature (4
). Although our findings did not reach significance regarding the effect of our healthy pattern on the risk of colorectal tumors, the observed trend toward lower risks is consistent with a protective effect of fruit and vegetables on the risk of colorectal tumors (2
). Vegetables and fruit are rich in fiber, antioxidant vitamins, folic acid, carotenoids, and other phytochemical compounds, which may yield beneficial properties and act in a synergic way against colorectal carcinogenesis.
In conclusion, our findings are consistent with a deleterious effect of patterns associated with a Western way of life—high in fats, animal products, and snacks and low in products of vegetable origin—on colorectal carcinogenesis. We observed some differences between the patterns associated with adenomas and those with cancer; this is not unexpected, as some cancers may not arise from an adenoma, and only a limited proportion of subjects with adenomas will eventually have cancer. Among subjects with Western dietary habits, those with a high meat intake may be particularly at risk of malignant transformation. These patterns may help to identify groups at high risk for whom prevention strategies may be particularly relevant.