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Metabolic Dysfunction, Obesity, and Survival Among Patients With Early-Stage Colorectal Cancer
Elizabeth M Cespedes Feliciano1, Candyce H Kroenke1, Jeffrey A Meyerhardt1
1Elizabeth M. Cespedes Feliciano, Candyce H. Kroenke, Marilyn L. Kwan, Charles Quesenberry, Erin K. Weltzien, Adrienne L. Castillo, and Bette J. Caan, Kaiser Permanente Northern California, Oakland; Patrick T. Bradshaw, School of Public Health, University of California, Berkeley, Berkeley, CA; Jeffrey A. Meyerhardt, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA; Carla M. Prado and Jingjie Xiao, University of Alberta, Edmonton, Alberta, Canada; and Andrew J. Dannenberg, Weill Cornell Medical College, New York, New York.
Purpose:
The effects of obesity and metabolic dysregulation on cancer survival are inconsistent. To identify high-risk subgroups of obese patients and to examine the joint association of metabolic syndrome (MetSyn) in combination with obesity, we categorized patients with early-stage (I to III) colorectal cancer (CRC) into four metabolic categories defined by the presence of MetSyn and/or obesity and examined associations with survival.
Methods:
We studied 2,446 patients diagnosed from 2006 to 2011 at Kaiser Permanente. We assumed MetSyn if patients had three or more of five components present at diagnosis: fasting glucose > 100 mg/dL or diabetes; elevated blood pressure (systolic ≥ 130 mm Hg, diastolic ≥ 85 mm Hg, or antihypertensives); HDL cholesterol < 40 mg/dL (men) or < 50 mg/dL (women); triglycerides ≥ 150 mg/dL or antilipids; and/or highest sex-specific quartile of visceral fat by computed tomography scan (in lieu of waist circumference). We then classified participants according to the presence (or absence) of MetSyn and obesity (BMI < 30 or ≥ 30 kg/m2) and assessed associations with overall and CRC-related survival using Cox proportional hazards models adjusted for demographic, tumor, and treatment factors and muscle mass at diagnosis.
Results:
Over a median follow-up of 6 years, 601 patients died, 325 as a result of CRC. Mean (SD) age was 64 (11) years. Compared with the reference of nonobese patients without MetSyn (n = 1,225), for overall survival the hazard ratios (HR) and 95% CIs were 1.45 (1.12 to 1.82) for obese patients with MetSyn (n = 480); 1.09 (0.83 to 1.44) for the nonobese with MetSyn (n = 417), and 1.00 (0.80 to 1.26) for obese patients without MetSyn (n = 324). Obesity with MetSyn also predicted CRC-related survival: 1.49 (1.09 to 2.02). The hazard of death increased with the number of MetSyn components present, independent of obesity.
Conclusion:
Patients with early-stage CRC with obesity and MetSyn have worse survival, overall and CRC related.
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