The Importance of Body Composition in Explaining the Overweight Paradox in Cancer-Counterpoint

Abstract

Despite a greater risk of cancer associated with higher BMI, overweight (BMI 25-<30 kg/m²) and class I obese (BMI 30-<35 kg/m²) patients often have a paradoxically lower risk of overall mortality after a cancer diagnosis, a phenomenon called the "obesity paradox." Only when patients exceed a BMI ≥35 kg/m² are elevations in mortality risk consistently noted. This paradox has been dismissed as the result of methodologic bias, which we will describe and debate here. However, even if such bias influences associations, there is growing evidence that body composition may in part explain the paradox. This phenomenon may more accurately be described as a BMI paradox. That is, BMI is a poor proxy for adiposity and does not distinguish muscle from adipose tissue, nor describe adipose tissue distribution. Low muscle mass is associated with higher risk of recurrence, overall and cancer-specific mortality, surgical complications, and treatment-related toxicities. Patients with who are overweight or obese have on average higher levels of muscle than their normal-weight counterparts. Also, there is some evidence that patients with moderate levels of subcutaneous adipose tissue may have lower mortality. More research utilizing body composition is needed to clarify the effects of adiposity on cancer mortality. Cancer Res; 78(8); 1906-12. ©2018 AACR.

Figure 1

Two Female Patients with Identical Overweight Body Mass Index (BMI 29kg/m²) and Different Body Compositions

Figure 2

A and B: Adapted from Caan et al, reference . Cubic spline for body mass index (BMI) has 4 knots and a reference value of BMI=27; adjusted for age, sex, race, stage, grade, site, treatment, pre-diagnosis BMI, smoking and physical activity; P<0.001 (test for non-linearity) (2A); and accompanying Histogram of Body Composition Phenotypes by BMI (2B)