Analysis of Body Mass Index and Mortality in Patients With Colorectal Cancer Using Causal Diagrams

Abstract

Importance: Physicians and investigators have sought to determine the relationship between body mass index (BMI [calculated as weight in kilograms divided by height in meters squared]) and colorectal cancer (CRC) outcomes, but methodologic limitations including sampling selection bias, reverse causality, and collider bias have prevented the ability to draw definitive conclusions.

Objective: To evaluate the association of BMI at the time of, and following, colorectal cancer (CRC) diagnosis with mortality in a complete population using causal diagrams.

Design, setting, and participants: This retrospective observational study with prospectively collected data included a cohort of 3408 men and women, ages 18 to 80 years, from the Kaiser Permanente Northern California population, who were diagnosed with stage I to III CRC between 2006 and 2011 and who also had surgery.

Exposures: Body mass index at diagnosis and 15 months following diagnosis.

Main outcomes and measures: Hazard ratios (HRs) for all-cause mortality and CRC-specific mortality compared with normal-weight patients, adjusted for sociodemographics, disease severity, treatment, and prediagnosis BMI.

Results: This study investigated a cohort of 3408 men and women ages 18 to 80 years diagnosed with stage I to III CRC between 2006 and 2011 who also had surgery. At-diagnosis BMI was associated with all-cause mortality in a nonlinear fashion, with patients who were underweight (BMI <18.5; HR, 2.65; 95% CI, 1.63-4.31) and patients who were class II or III obese (BMI ≥35; HR, 1.33; 95% CI, 0.89-1.98) exhibiting elevated mortality risks, compared with patients who were low-normal weight (BMI 18.5 to <23). In contrast, patients who were high-normal weight (BMI 23 to <25; HR, 0.77; 95% CI, 0.56-1.06), low-overweight (BMI 25 to <28; HR, 0.75; 95% CI, 0.55-1.04), and high-overweight (BMI 28 to <30; HR, 0.52; 95% CI, 0.35-0.77) had lower mortality risks, and patients who were class I obese (BMI 30 to <35) showed no difference in risk. Spline analysis confirmed a U-shaped relationship in participants with lowest mortality at a BMI of 28. Associations with CRC-specific mortality were similar. Associations of postdiagnosis BMI and mortality were also similar, but patients who were class I obese had significantly lower all-cause and cancer-specific mortality risks.

Conclusions and relevance: In this study, body mass index at the time of diagnosis and following diagnosis of CRC was associated with mortality risk. Though evidence shows that exercise in patients with cancer should be encouraged, findings suggest that recommendations for weight loss in the immediate postdiagnosis period among patients with CRC who are overweight may be unwarranted.

Figure 1

Spline curve of BMI at diagnosis and overall mortality, p-value, test for nonlinearity <0.0001. Adjusted for age, sex, race, stage, site, grade, chemotherapy, radiation, pre-diagnosis BMI, smoking, and physical activity.