Importance
Physicians and investigators have sought to determine the relationship between body mass index (BMI) 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
We evaluated the impact of BMI at the time of, and following colorectal cancer (CRC) diagnosis, on mortality in a complete population using causal diagrams.
Design
Retrospective observational study with prospectively collected data
Setting
Kaiser Permanente Northern California
Participants
3,408 men and women diagnosed 2006-2011 with stages I-III colorectal cancer who had surgery
Exposures
BMI at diagnosis, and 15 months following diagnosis
Main Outcomes and Measures
Hazard ratios for all-cause and CRC-specific mortality, relative to normal-weight patients, adjusted for sociodemographics, disease severity, treatment, and pre-diagnosis BMI.
Results
At-diagnosis BMI was associated with all-cause mortality in a nonlinear fashion, with underweight (BMI<18.5 kg/m2, hazard ratio [HR]=2.65, 95% confidence interval [CI]:1.63-4.31) and class II/III obese (BMI≥35 kg/m2, HR=1.33, 95% CI: 0.89-1.98) patients exhibiting elevated mortality risks, compared with low normal-weight (BMI 18.5-<23 kg/m2) patients. In contrast, high-normal-weight (BMI 23-<25 kg/m2, HR=0.77, 95% CI: 0.56-1.06), low-overweight (BMI 25-<28 kg/m2, HR=0.75, 95% CI:0.55-1.04), and high-overweight (BMI 28-<30 kg/m2, HR=0.52, 95% CI: 0.35-0.77) patients had lower mortality risks, and class I obese (BMI 30-<35 kg/m2) patients showed no difference in risk. Spline analysis confirmed a U-shaped relationship in participants (p-value, test for nonlinearity<0.001) with lowest mortality at BMI=28 kg/m2. Associations with CRC-specific mortality were similar. Associations of post-diagnosis BMI and mortality were also similar, but class I obese had significantly lower all-cause and cancer-specific mortality risks.
Conclusions and Relevance
Overweight patients consistently had the lowest mortality after a CRC diagnosis. Though strong scientific evidence shows that exercise in cancer patients should be encouraged, findings suggest, among overweight CRC patients, that recommendations for weight loss in the immediate post-diagnosis period may be unwarranted.