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

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

  2. Author Address

    Division of Cancer Epidemiology and Genetics, NIH, DHHS, National Cancer Institute, Rockville, Maryland, USA., Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Department of Oncology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, Michigan, USA., Department of Epidemiology and Biostatistics, Imperial College London, London, UK., Southwest Oncology Group (SWOG) Statistics & Data Management Center (SDMC), Fred Hutchinson Cancer Research Center, Seattle, Washington, USA., Swedish Medical Center, Swedish Cancer Institute, Seattle, Washington, USA., Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA., Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK., Department of Public Health and Primary Care, American Cancer Society Inc, Atlanta, Georgia, USA., CESP, Fac. de m 233;decine - Univ. Paris-Sud, Fac. de m 233;decine - UVSQ, INSERM, Universit 233; Paris-Saclay, Paris, France., Generations and Health, Gustave Roussy, Villejuif, France., Department of Community Medicine, UiT The Arctic University of Norway, Tromso, Norway., Department of Surgical and Perioperative Sciences, Umea University, Umea, Sweden., Information Management Services (IMS), Rockville, Maryland, USA., Human Papilloma Virus (HPV) Immunology Laboratory, Frederick National Laboratory for Cancer Research, Frederick, Maryland, USA., Division of Research, Kaiser Permanente Northern California, Oakland, California, USA., Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii, USA., Prevention and Implementation Group, International Agency for Research on Cancer, Lyon, France.,
    1. Year: 2019
    2. Date: JUN
    3. Epub Date: 2018 08 18
  2. Journal: Gut
    1. 68
    2. 6
    3. Pages: 960-968
  4. Type of Article: Article
  5. ISSN: 0017-5749
  1. Abstract:

    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. 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. Soluble tumour necrosis factor receptor 2 (sTNFR2) (ORsquartile 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. 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. © Author(s) (or their employer(s)) 2018. No commercial re-use. See rights and permissions. Published by BMJ.

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External Sources

  1. View Full Text
  2. DOI: 10.1136/gutjnl-2018-316678
  3. PMID: 30121626
  4. View record in Web of Science®
  5. WOS: 000471832900004
  6. PII : gutjnl-2018-316678

Library Notes

  1. Fiscal Year: FY2017-2018
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