The Association of Abdominal Adiposity With Mortality in Patients With Stage I–III Colorectal Cancer

Justin C. Brown; Bette J. Caan; Carla M. Prado; Elizabeth M. Cespedes Feliciano; Jingjie Xiao; Candyce H. Kroenke; Jeffrey A. Meyerhardt

Disclosures

J Natl Cancer Inst. 2020;112(4):377-383. 

In This Article

Abstract and Introduction

Abstract

Background: The quantity and distribution of adipose tissue may be prognostic measures of mortality in colorectal cancer patients, and such associations may vary by patient sex.

Methods: This cohort included 3262 stage I–III colorectal cancer patients. Visceral and subcutaneous adipose tissues were quantified using computed tomography. The primary endpoint was all-cause mortality. Restricted cubic splines estimated statistical associations with two-sided P values.

Results: Visceral adipose tissue was prognostic of mortality in a reverse L-shaped pattern (nonlinear P = .02); risk was flat to a threshold (~260 cm2) then increased linearly. Subcutaneous adipose tissue was prognostic of mortality in a J-shaped pattern (nonlinear P < .001); risk was higher at extreme (<50 cm2) but lower at intermediate values (>50 to ≤560 cm2). Patient sex modified the prognostic associations between visceral adipose tissue (P interaction = .049) and subcutaneous adipose tissue (P interaction = .04) with mortality. Among men, visceral adiposity was associated with mortality in a J-shaped pattern (nonlinear P = .003), whereas among women, visceral adiposity was associated with mortality in a linear pattern (linear P = .008). Among men, subcutaneous adiposity was associated with mortality in an L-shaped pattern (nonlinear P = .01), whereas among women, subcutaneous adiposity was associated with mortality in a J-shaped pattern (nonlinear P < .001).

Conclusions: Visceral and subcutaneous adipose tissue were prognostic of mortality in patients with colorectal cancer; the shape of these associations were often nonlinear and varied by patient sex. These results offer insight into the potential biological mechanisms that link obesity with clinical outcomes in patients with cancer, suggesting that the dysregulated deposition of excess adiposity is prognostic of mortality.

Introduction

Body mass index (BMI) is a surrogate measure for total body adiposity.[1] In a pooled analysis of 25 291 patients with early-stage colon cancer, men with class II or III obesity (BMI ≥35.0 kg/m2) were 16% more likely to die compared with men of normal weight (BMI 18.5–24.9 kg/m2); however, no such association was observed in women.[2] BMI does not distinguish muscle from adiposity, nor does it differentiate visceral and subcutaneous adipose tissue regions.[3] Men preferentially store adiposity viscerally, whereas women store adiposity subcutaneously.[4] Visceral adiposity secretes a variety of protumorigenic metabolites relative to subcutaneous adiposity,[5–7] which may explain, in part, why BMI is prognostic in men but not in women.[8]

The quantity and distribution of adipose tissue may be powerful prognostic measures of mortality in patients with colorectal cancer.[9,10] However, studies to date have offered conflicting insight,[11] concluding that excess visceral adiposity increases,[12] decreases,[13] or has no influence[14,15] on the risk of poor clinical outcomes. Emerging evidence also suggests that excess subcutaneous adiposity decreases the risk of poor clinical outcome.[16,17] Adiposity is correlated with muscle, and it is not known if the prognostic effects of adipose tissue quantity and distribution are independent of muscle.[18] The current study tested the hypothesis that visceral and subcutaneous adipose tissue, measured using abdominal computed tomography (CT) imaging, are prognostic of mortality in 3262 patients with stage I–III colorectal cancer and that such prognostic associations are modified by patient sex.

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