Explaining the Obesity Paradox: The Association between Body Composition and Colorectal Cancer Survival (C-SCANS Study)

Abstract

Background: Body composition may partially explain the U-shaped association between body mass index (BMI) and colorectal cancer survival.Methods: Muscle and adiposity at colorectal cancer diagnosis and survival were examined in a retrospective cohort using Kaplan-Meier curves, multivariable Cox regression, and restricted cubic splines in 3,262 early-stage (I-III) male (50%) and female (50%) patients. Sarcopenia was defined using optimal stratification and sex- and BMI-specific cut points. High adiposity was defined as the highest tertile of sex-specific total adipose tissue (TAT). Primary outcomes were overall mortality and colorectal cancer-specific mortality (CRCsM).Results: Slightly over 42% patients were sarcopenic. During 5.8 years of follow-up, 788 deaths occurred, including 433 from colorectal cancer. Sarcopenic patients had a 27% [HR, 1.27; 95% confidence interval (CI), 1.09-1.48] higher risk of overall mortality than those who were not sarcopenic. Females with both low muscle and high adiposity had a 64% higher risk of overall mortality (HR, 1.64; 95% CI, 1.05-2.57) than females with adequate muscle and lower adiposity. The lowest risk of overall mortality was seen in patients with a BMI between 25 and <30 kg/m², a range associated with the greatest number of patients (58.6%) who were not at increased risk of overall mortality due to either low muscle or high adiposity.Conclusions: Sarcopenia is prevalent among patients with non-metastatic colorectal cancer, and should, along with adiposity be a standard oncological marker.Impact: Our findings suggest a biologic explanation for the obesity paradox in colorectal cancer and refute the notion that the association between overweight and lower mortality is due solely to methodologic biases. Cancer Epidemiol Biomarkers Prev; 26(7); 1008-15. ©2017 AACR.

Figure 1

A Kaplan-Meier curves for sarcopenia and all-cause mortality B Kaplan-Meier curves for body composition phenotypes and all-cause mortality

Figure 2

Restricted cubic splines for body composition and overall mortality, by sex. Reference is sex-specific median; graphs have 4 knots and are truncated at 1^st and 99^th percentiles; adjusted for age, stage, site, treatment and partitioned BMI. SMI graphs additionally adjusted for total adiposity in tertiles; total adiposity graphs adjusted for muscle in tertiles.

Figure 3

A Restricted cubic spline for BMI has 4 knots and a reference value of 27; adjusted for age, sex, race, stage, grade, site, treatment, pre-diagnosis BMI, smoking and physical activity. Reference value is the overall median (27.2); test for curvature p < 0.0001; overall significance p < 0.0001. B Histogram for body composition phenotypes by BMI