title: Joint prognostic effect of obesity and chronic systemic inflammation in patients with metastatic colorectal cancer.
abstract: BACKGROUND
  Obesity is strongly linked with chronic systemic inflammation, and each has been linked with disease progression and survival in patients with colorectal cancer (CRC). The authors investigated the joint prognostic effects of obesity and circulating cytokines in patients with metastatic CRC (mCRC), an understudied patient group.
  
  
  METHODS
  In 242 chemotherapy-naive patients with mCRC, the authors measured a multiplex cytokine panel and abstracted clinicopathological features, height, and weight from medical records. Overall survival (OS) was calculated from the date of mCRC diagnosis until the date of death from any cause and evaluated by Kaplan-Meier analysis and multivariable Cox proportional hazards regression models. Cut points for cytokines were determined by restricted cubic spline regression.
  
  
  RESULTS
  In multivariable models, elevated interleukin (IL)-8, IL-2 receptor alpha, and lactate dehydrogenase (LDH) emerged as significant predictors of poor OS (hazard ratio [HR] and 95% confidence interval [95% CI] for above vs below the (referent) knot point: 2.5 [95% CI, 1.7-3.7], 1.9 [95% CI, 1.3-2.7], and 2.2 [95% CI, 1.6-3.1], respectively; all P<.001). Obesity (body mass index ≥30 kg/m(2) ) was not found to be associated with OS, but appeared to modify the relationships observed with IL-8 and LDH, which were associated with a significant 4-fold and 5-fold risk of death, respectively, in obese patients compared with a 2-fold risk of death in nonobese patients (P for interaction of .06 and .04, respectively). Similar results emerged from joint effects analysis, in which obese patients with high IL-8 (or LDH) experienced the highest risk of death.
  
  
  CONCLUSIONS
  Although obesity itself was not found to be independently associated with survival in patients with mCRC, the adverse prognostic significance of LDH and IL-8 was found to be enhanced in obese patients.
authors.affiliation: Division of OVP, Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.|Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas.
authors.forename: Manasi S
authors.initials: MS
authors.lastname: Shah
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: David R
authors.initials: DR
authors.lastname: Fogelman
authors.affiliation: Division of Epidemiology, Human Genetics and Environmental Sciences, The University of Texas School of Public Health, Houston, Texas.
authors.forename: Kanwal Pratap Singh
authors.initials: KP
authors.lastname: Raghav
authors.affiliation: Division of Cancer Medicine, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: John V
authors.initials: JV
authors.lastname: Heymach
authors.affiliation: Division of Cancer Medicine, Department of Thoracic/Head and Neck Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hai T
authors.initials: HT
authors.lastname: Tran
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Zhi-Qin
authors.initials: ZQ
authors.lastname: Jiang
authors.affiliation: Division of Cancer Medicine, Department of Gastrointestinal Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Scott
authors.initials: S
authors.lastname: Kopetz
authors.affiliation: Division of OVP, Cancer Prevention and Population Sciences, Department of Epidemiology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Carrie R
authors.initials: CR
authors.lastname: Daniel
mesh_terms: D015179:Colorectal Neoplasms / Q000097:blood / Q000401:mortality / Q000473:pathology*; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009765:Obesity / Q000097:blood* / Q000401:mortality / Q000473:pathology; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: D016207:Cytokines
keywords: body mass index; inflammation; interleukin-8; lactate dehydrogenase; metastatic colorectal cancer; mortality; obesity