An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma Journal Article


Authors: Hakimi, A. A.; Furberg, H.; Zabor, E. C.; Jacobsen, A.; Schultz, N.; Ciriello, G.; Mikkilineni, N.; Fiegoli, B.; Kim, P. H.; Voss, M. H.; Shen, H.; Laird, P. W.; Sander, C.; Reuter, V. E.; Motzer, R. J.; Hsieh, J. J.; Russo, P.
Article Title: An epidemiologic and genomic investigation into the obesity paradox in renal cell carcinoma
Abstract: BackgroundObesity 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.MethodsData 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.ResultsObese 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.ConclusionsOur 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. © 2013 The Author .
Journal Title: JNCI: Journal of the National Cancer Institute
Volume: 105
Issue: 24
ISSN: 0027-8874
Publisher: Oxford University Press  
Date Published: 2013-12-18
Start Page: 1862
End Page: 1870
Language: English
DOI: 10.1093/jnci/djt310
PROVIDER: scopus
PMCID: PMC3866155
PUBMED: 24285872
DOI/URL:
Notes: Cited By (since 1996):1 -- Export Date: 3 February 2014 -- CODEN: JNCIA -- Source: Scopus
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MSK Authors
  1. Paul Russo
    458 Russo
  2. Robert Motzer
    771 Motzer
  3. Martin Henner Voss
    130 Voss
  4. Emily Craig Zabor
    136 Zabor
  5. James J Hsieh
    114 Hsieh
  6. Chris Sander
    196 Sander
  7. Victor Reuter
    926 Reuter
  8. Philip Hyunwoo Kim
    39 Kim
  9. Nikolaus D Schultz
    206 Schultz
  10. Abraham Ari Hakimi
    134 Hakimi