Eating Frequency, Diet Quality, and Colorectal Cancer Risk
In this cohort of 34,968 men, the majority ate 3 times/day (47.8%) or 4 times/day (33.8%), and fewer ate more frequently (5–8 meals/day; 7.9%) or less frequently (1–2 times/day; 10.5%). Men who ate less frequently mostly skipped breakfast (71%) or lunch (51%), ate more at dinner time (89%), smoked more, took fewer aspirin, multivitamins, and antioxidant supplements, drank more alcohol, consumed fewer calories, and had a lower intake of all measured nutrients and foods in general (Table 1). The positive association observed between DASH score and eating frequency (r = 0.14) was mainly driven by the positive association between eating frequency and intakes of whole grains (r = 0.14), low-fat dairy (r = 0.11), and fruits (r = 0.10), which were also positively associated with DASH score.
No statistically significant association was found between increased eating frequency, increased snack frequency, or breakfast pattern and the incidence of CRC or colon cancer. After adjusting for the known risk factors for CRC, results were close to the age-adjusted values, and the observed 12% lower risk of CRC and the 22% lower risk of colon cancer were not statistically significant when comparing persons in the highest eating frequency category (5–8 times/day) with those in the reference category (3 times/day) (Table 2). Further, no association was observed when comparing persons in the highest snack frequency category (2–4 snacks/day) with those in the lowest (0 snacks/day) for CRC and colon cancer risk (Table 3). Similarly, no statistically significant association was found with CRC and colon cancer risk when comparing participants who skipped breakfast and ate 1–7 times/day with persons who regularly had breakfast and ate 1–3 or 4–8 other times per day (Table 4). The results remained unchanged when participants who did not consume breakfast and ate 1–7 times per day were further broken down into 3 groups: persons who ate 1–2 times/day, persons who ate 3 times/day, and persons who ate 4–7 times/day (data not shown). All of these associations remained unchanged after further adjustment for coffee intake and glycemic load (data not shown).
We then examined interactions with dietary patterns. An inverse association between meal frequency and CRC risk was suggested primarily in persons with a high DASH score (P for trend = 0.14; P for interaction = 0.01) (Figure 1A) and in persons with a low-glycemic-load diet (all relative risks <1 for the low glycemic load stratum), although the interaction was not significant (P for trend = 0.94, P for interaction = 0.99; data not shown). As for the factors associated with insulin sensitivity, the inverse association between increased eating frequency and CRC risk was stronger in participants who were highly insulin sensitive (i.e., coffee intake ≥2 cups/day) (P for trend = 0.25, P for interaction = 0.20; data not shown), had a physical activity level higher than the median value (P for trend = 0.13, P for interaction = 0.04; Figure 1B), and had a BMI <25 (P for trend = 0.04, P for interaction = 0.07; Figure 1C). Moreover, when these 3 insulin-sensitivity variables were combined, the inverse association was observed only in the high-insulin-sensitivity group (P for trend = 0.01, P for interaction < 0.01; Figure 1D).
Associations between colorectal cancer and other variables in 34,968 US men from the Health Professional Follow-up Study, 1992–2006. Values are hazard ratios from Cox proportional hazards models. All tests were 2-sided. A) Joint association between eating frequency and Dietary Approaches to Stop Hypertension (DASH) score and colorectal cancer risk (P for interaction = 0.01). Multivariate models were adjusted for age (in months), aspirin use (≥2 times per week, <2 times per week, or missing), family history of colorectal cancer (yes, no, or missing), previous endoscopy (screening in the past 2 years, never, or missing), use of supplements containing antioxidants (ever, never, or missing), body mass index (BMI, measured as weight (kg)/height (m); 24, 24–26.0, 26.1–29, or >29), energy intake (kilocalories/day, continuous), alcohol intake (0, 0.1–4.9, 5–14.9, or ≥15 g/day), physical activity level (quintile of metabolic equivalent hours/week), red meat consumption (quintile of servings/day), total calcium intake (quintile of mg/day), dietary folate intake (quintile of μg/day), dietary vitamin D intake (quintile of IU/day), pack years of smoking before 30 years of age (continuous or missing indicator), race (white, nonwhite, or missing), and DASH score (continuous) together with eating frequency (continuous). B) Joint association between eating frequency and physical activity level and colorectal cancer risk (P for interaction = 0.04). The same adjustments were made to the model as in A, except that physical activity level (median of deciles) was combined with eating frequency (continuous). C) Joint association between eating frequency and BMI with colorectal cancer risk (P for interaction = 0.07). The same adjustments were made to the model as in A, except that BMI (median of deciles) was combined with eating frequency (continuous). D) Joint association between eating frequency and insulin resistance score and colorectal cancer risk (P for interaction < 0.01). The same adjustments were made to the model as in A, except that physical activity level and BMI were omitted. The insulin sensitivity score consisted of the 3 combined variables (coffee intake, physical activity level, and BMI) and was categorized into 2 groups (0–1 vs. 2–3), such that a higher score denoted less insulin sensitivity (i.e., a relatively insulin-sensitive individual would get the highest score of 3 and an insulin-resistant person would get the worst score of 0). Bars and numbers in parentheses, 95% confidence intervals.
Additionally, the implied decreased association between increased snack frequency (2–4 snacks/day) and the risk of CRC or colon cancer was only observed among participants whose diets fell in the higher DASH score category (data not shown), who drank 2 or more cups of coffee per day (data not shown), who were more physically active (data not shown), or who had a lower BMI (data not shown). The only exception was glycemic load. As for breakfast consumption pattern, the joint analysis revealed no particular benefit for participants who consumed breakfast and who were either in the high DASH score category, the low glycemic load category, the coffee drinkers category, the more physically active group, or the lower BMI category when compared with persons who skipped breakfast and fell within a category opposite of one of those mentioned (data not shown). For the above multivariate relative risks derived from the basic multivariate model that included the standard risk factor for CRC and DASH score, further adjustment for coffee intake and glycemic load did not modify the results; therefore, the results are not shown.