Prediagnostic circulating markers of inflammation and risk of oesophageal adenocarcinoma: A study within the National Cancer Institute Cohort Consortium

Michael B. Cook, Matthew J. Barnett, Cathryn H. Bock, Amanda J. Cross, Phyllis J. Goodman, Gary E. Goodman, Christopher A. Haiman, Kay Tee Khaw, Marjorie L. McCullough, Christine C. Newton, Marie Christine Boutron-Ruault, Eiliv Lund, Martin Rutegård, Mark D. Thornquist, Michael Spriggs, Carol Giffen, Neal D. Freedman, Troy Kemp, Candyce H. Kroenke, Loïc Le MarchandJin Young Park, Michael Simon, Lynne R. Wilkens, Ligia Pinto, Allan Hildesheim, Peter T. Campbell

Research output: Contribution to journalArticlepeer-review

17 Scopus citations


Objective Cross-sectional data indicate that systemic inflammation is important in oesophageal adenocarcinoma. We conducted a prospective study to assess whether prediagnostic circulating markers of inflammation were associated with oesophageal adenocarcinoma and to what extent they mediated associations of obesity and cigarette smoking with cancer risk. Design This nested case-control study included 296 oesophageal adenocarcinoma cases and 296 incidence density matched controls from seven prospective cohort studies. We quantitated 69 circulating inflammation markers using Luminex-based multiplex assays. Conditional logistic regression models estimated associations between inflammation markers and oesophageal adenocarcinoma, as well as direct and indirect effects of obesity and smoking on risk of malignancy. Results Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORs quartile 4 vs 1 =2.67, 95% CI 1.52 to 4.68) was significantly associated with oesophageal adenocarcinoma. Additional markers close to the adjusted significance threshold included C reactive protein, serum amyloid A, lipocalin-2, resistin, interleukin (IL) 3, IL17A, soluble IL-6 receptor and soluble vascular endothelial growth factor receptor 3. Adjustment for body mass index, waist circumference or smoking status slightly attenuated biomarker-cancer associations. Mediation analysis indicated that sTNFR2 may account for 33% (p=0.005) of the effect of waist circumference on oesophageal adenocarcinoma risk. Resistin, plasminogen activator inhibitor 1, C reactive protein and serum amyloid A were also identified as potential mediators of obesity-oesophageal adenocarcinoma associations. For smoking status, only plasminogen activator inhibitor 1 was a nominally statistically significant (p<0.05) mediator of cancer risk. Conclusion This prospective study provides evidence of a link between systemic inflammation and oesophageal adenocarcinoma risk. In addition, this study provides the first evidence that indirect effects of excess adiposity and cigarette smoking, via systemic inflammation, increase the risk of oesophageal adenocarcinoma.

Original languageEnglish (US)
Pages (from-to)960-968
Number of pages9
Issue number6
StatePublished - Jun 1 2019
Externally publishedYes


  • cancer epidemiology
  • inflammation
  • inflammatory mediators
  • oesophageal cancer

ASJC Scopus subject areas

  • Gastroenterology


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