title: An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma.
abstract: BACKGROUND
  Obesity increases risk for clear-cell renal cell carcinoma (ccRCC), yet obese patients appear to experience longer survival than nonobese patients. We examined body mass index (BMI) in relation to stage, grade, and cancer-specific mortality (CSM) while considering detection bias, nutritional status, and molecular tumor features.
  
  
  METHODS
  Data were available from 2119 ccRCC patients who underwent renal mass surgery at Memorial Sloan-Kettering Cancer Center between 1995 and 2012. Logistic regression models produced associations between BMI and advanced disease. Multivariable competing risks regression models estimated associations between BMI and CSM. Somatic mutation, copy number, methylation, and expression data were examined by BMI among a subset of 126 patients who participated in the Cancer Genome Atlas Project for ccRCC using the Kruskal-Wallis or Fisher exact tests. All statistical tests were two-sided.
  
  
  RESULTS
  Obese and overweight patients were less likely to present with advanced-stage disease compared with normal-weight patients (odds ratio [OR] = 0.61, 95% confidence interval [CI] = 0.48 to 0.79 vs OR = 0.65, 95% CI = 0.51 to 0.83, respectively). Higher BMI was associated with reduced CSM in univariable analyses (P < .005). It remained statistically significant after adjustment for comorbidities and albumin level, but it became non-statistically significant after adjusting for stage and grade (P > .10). Genome-wide interrogation by BMI suggested differences in gene expression of metabolic and fatty acid genes, including fatty acid synthase (FASN), consistent with the obesity paradox.
  
  
  CONCLUSIONS
  Our findings suggest that although BMI is not an independent prognostic factor for CSM after controlling for stage and grade, tumors developing in an obesogenic environment may be more indolent.
authors.affiliation: Affiliations of authors: Urology Service, Department of Surgery (AAH, NM, BF, PHK, PR), Human Oncology & Pathogenesis Program (AAH, JJH); Epidemiology and Biostatistics (HF, ECZ), Computational Biology (AJ, NS, GC, CS), Genitourinary Oncology (MHV, RJM, JJH), and Department of Pathology (VER), Memorial Sloan-Kettering Cancer Center, New York, NY; USC Epigenome Center, University of Southern California, Los Angeles, California (HS, PWL); Weill Medical College, Cornell University, New York, NY (RJM, JJH, PR).
authors.forename: A Ari
authors.initials: AA
authors.lastname: Hakimi
authors.forename: Helena
authors.initials: H
authors.lastname: Furberg
authors.forename: Emily C
authors.initials: EC
authors.lastname: Zabor
authors.forename: Anders
authors.initials: A
authors.lastname: Jacobsen
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Schultz
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciriello
authors.forename: Nina
authors.initials: N
authors.lastname: Mikklineni
authors.forename: Brandon
authors.initials: B
authors.lastname: Fiegoli
authors.forename: Philip H
authors.initials: PH
authors.lastname: Kim
authors.forename: Martin H
authors.initials: MH
authors.lastname: Voss
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Peter W
authors.initials: PW
authors.lastname: Laird
authors.forename: Chris
authors.initials: C
authors.lastname: Sander
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reuter
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Motzer
authors.forename: James J
authors.initials: JJ
authors.lastname: Hsieh
authors.forename: Paul
authors.initials: P
authors.lastname: Russo
mesh_terms: D000328:Adult; D000368:Aged; D015992:Body Mass Index; D002292:Carcinoma, Renal Cell / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D056915:DNA Copy Number Variations; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D016015:Logistic Models; D008297:Male; D008499:Medical Records; D008875:Middle Aged; D009154:Mutation; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009519:New York City / Q000453:epidemiology; D009765:Obesity / Q000150:complications* / Q000453:epidemiology / Q000235:genetics; D016017:Odds Ratio; D050177:Overweight / Q000150:complications; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis