The Joint Association of Eating Frequency and Diet Quality With Colorectal Cancer Risk in the Health Professionals Follow-up Study

Rania A. Mekary; Frank B. Hu; Walter C. Willett; Stephanie Chiuve; Kana Wu; Charles Fuchs; Teresa T. Fung; Edward Giovannucci


Am J Epidemiol. 2012;175(7):664-672. 

In This Article

Abstract and Introduction


The results of most case-control studies have suggested a positive association between eating frequency and colorectal cancer risk. Because no prospective cohort studies have done so to date, the authors prospectively examined this association. In 1992, eating frequency was assessed in a cohort of 34,968 US men in the Health Professionals Follow-up Study. Cox proportional hazards regression models were used to estimate relative risks and 95% confidence intervals for various levels of eating frequency. Effect modifications by overall dietary quality (assessed using the Diet Approaches to Stop Hypertension score) and by factors that influence insulin resistance were further assessed. Between 1992 and 2006, a total of 583 cases of colorectal cancer were diagnosed. When comparing the highest eating frequency category (5–8 times/day) with the reference category (3 times/day), the authors found no evidence of an increased risk of colorectal cancer (multivariate relative risk = 0.88, 95% confidence interval: 0.62, 1.26) or colon cancer (multivariate relative risk = 0.78, 95% confidence interval: 0.49, 1.25). There was an implied inverse association with eating frequency among participants who had healthier diets (high Diet Approaches to Stop Hypertension score; P for interaction = 0.01), especially among men in the high-insulin-sensitivity group (body mass index (weight (kg)/height (m)2) <25, ≥2 cups of coffee/day, and more physical activity; P for interaction < 0.01, P for trend = 0.01). There was an implied protective association between increased eating frequency of healthy meals and colorectal cancer risk and in men with factors associated with higher insulin sensitivity.


Colorectal cancer (CRC) is the third leading cause of cancer death in both the United States[1] and worldwide.[2] Findings from most case-control studies have suggested that CRC risk increases with higher eating frequency (meals and/or snacks),[3–8] although the results of 2 of these studies did not reach statistical significance.[3,4] Conversely, in 1 case-control study, de Verdier and Longnecker[9] found a null association between the risk of colon cancer and meal frequency but a positive association between the risk of colon cancer and snack frequency. In another case-control study, investigators found no association between CRC risk and snack frequency or eating frequency, but they did find a positive association with meal frequency.[10] On the basis of inconsistent results across studies and the case-control study design that may be subject to recall bias, no firm conclusion could be made regarding the influence of meal frequency on CRC risk. Examining this association between meal frequency and CRC risk prospectively is important to exclude potential reporting biases.

Further, if eating frequency is associated with CRC risk, it is reasonable to hypothesize that the association might be modified by dietary quality. The Dietary Approaches to Stop Hypertension (DASH) diet entails high intakes of fruits, vegetables, and legumes and nuts, moderate intakes of low-fat dairy products, and low intakes of animal protein and sweets, as well as reduced sodium intake.[11] Although the DASH diet was originally designed to aid in blood pressure reduction, adherence to this diet has previously been shown to be associated with a reduced risk of prevalent colorectal adenomas[12] and CRC.[13] Glycemic load, another variable that represents both the quality and the quantity of the carbohydrates consumed in a diet, also reflects dietary quality and has previously been associated with colon cancer risk in some studies.[14] Moreover, increased meal frequency could have a complex association with insulin secretion;[15] both high insulin secretion and insulin resistance increase the risk of CRC.[14] We prospectively examined data from the Health Professionals Follow-Up Study to determine whether meal frequency was associated with CRC risk and whether any association was modified by indicators of dietary quality (i.e., DASH score and glycemic load) and the major factors that influence insulin resistance, including coffee intake,[16] physical activity level,[17] and body mass index (BMI, measured as weight (kg)/height (m)2).


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