Metabolic Dysfunction, Obesity, and Survival Among Patients With Early-Stage Colorectal Cancer.
OBJECTIVE
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.


CONCLUSIONS
Patients with early-stage CRC with obesity and MetSyn have worse survival, overall and CRC related.
Elizabeth 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.
Elizabeth M
EM
Cespedes Feliciano
Elizabeth 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.
Candyce H
CH
Kroenke
Elizabeth 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.
Jeffrey A
JA
Meyerhardt
Elizabeth 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.
Carla M
CM
Prado
Elizabeth 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.
Patrick T
PT
Bradshaw
Elizabeth 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.
Andrew J
AJ
Dannenberg
Elizabeth 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.
Marilyn L
ML
Kwan
Elizabeth 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.
Jingjie
J
Xiao
Elizabeth 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.
Charles
C
Quesenberry
Elizabeth 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.
Erin K
EK
Weltzien
Elizabeth 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.
Adrienne L
AL
Castillo
Elizabeth 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.
Bette J
BJ
Caan