Background: It is unclear whether the increased risk of colon cancer associated with obesity differs for men and women, by distribution of body fat, or by location of the tumor. The primary goal of this study was to address these questions.

Methods: Eligible subjects from the Framingham Study cohort were classified according to body mass index (BMI) and waist size during two age periods: 30-54 y (n=3764) and 55-79 y (n=3802). All eligible men and women were cancer-free at baseline and had complete information on the following potential confounders: age, sex, education, height, activity, smoking, and alcohol. There were 157 incident lifetime cases of colon cancer among those followed beginning at 30-54 y of age and 149 lifetime cases among those whose follow up began at 55-79 y. Subjects were stratified further by gender, activity, and tumor location. The Cox Proportional Hazards Models were used to adjust for possible confounding by the above-described factors.

Results: A BMI >/=30 led to a 50% increased risk (95% CI: 0.92-2.5) of colon cancer among middle-aged (30-54 y) and a 2.4-fold increased risk (95% CI: 1.5-3.9) among older (55-79 y) adults. The BMI effect was stronger for men than for women and for cases occurring in the proximal colon. These adverse effects generally diminished when waist was added to the multivariable models. A larger waist size (>/=99.1 cm (39 in) and 101.6 cm (40 in) for women and men, respectively) was associated with a two-fold increased risk of colon cancer; this risk increased linearly with increasing waist size and was evident for both proximal and distal colon cancer. There was no attenuation of these effects when BMI was added to the multivariable models. A larger waist had a particularly adverse effect among sedentary subjects (relative risk (RR)=4.4 for middle-aged adults; RR=3.0 for older adults).

Conclusion: These findings suggest that waist circumference is a stronger predictor of colon cancer risk than is BMI, and that central obesity is responsible for an increased risk of cancer of both the proximal and distal colon.