Prediagnostic circulating inflammation markers and endometrial cancer risk in the prostate, lung, colorectal and ovarian cancer (PLCO) screening trial

Britton Trabert, Ronald C. Eldridge, Ruth M. Pfeiffer, Meredith S. Shiels, Troy J. Kemp, Chantal Guillemette, Patricia Hartge, Mark E. Sherman, Louise A. Brinton, Amanda Black, Anil K. Chaturvedi, Allan Hildesheim, Sonja I. Berndt, Mahboobeh Safaeian, Ligia Pinto, Nicolas Wentzensen

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Inflammation is proposed to increase risk of developing endometrial cancer, but few prospective epidemiologic studies have investigated the relationship between circulating inflammation markers and endometrial cancer risk. In a nested case-control study within the PLCO Screening Trial we measured serum levels of 64 inflammation-related biomarkers in 284 incident endometrial cancer cases and 284 matched controls. Using multivariable logistic regression inflammation markers were evaluated individually and combined into a cross-validated inflammation score. Of 64 markers, 22 were associated with endometrial cancer risk at p < 0.05 and 17 of 22 markers remained associated after multiple testing corrections. After adjusting for BMI and estradiol, SERPINE1 [quartile(Q)4 vs. Q1 odds ratio (OR) (95% confidence interval (CI)), p trend = 2.43 (0.94–6.29), 0.03] and VEGFA [2.56 (1.52–4.30), 0.0002] were positively associated with endometrial cancer risk, while CCL3 [0.46 (0.27–0.77), 0.01], IL13 [0.55 (0.33–0.93), 0.01], IL21 [0.52 (0.31–0.87), 0.01], IL1B [0.51 (0.30–0.86), 0.01] and IL23 [0.60 (0.35–1.03), 0.02] were inversely associated with risk. We observed large differences in ORs across BMI-inflammation score categories. Endometrial cancer risk was most pronounced among obese women with the highest inflammation score tertile (T) [10.25 (3.56–29.55) vs. normal BMI/T1]. Several inflammation markers were prospectively associated with endometrial cancer, including adipokines, pro- and anti-inflammatory cytokines, angiogenic factors and acute phase proteins. Inverse associations with anti-inflammatory markers (IL13, IL21), other inflammation markers/mediators (CCL3, IL1B, IL23), and a robust positive association between VEGFA and endometrial cancer risk were independent of BMI and estradiol, suggesting that these factors may influence risk through other mechanisms.

Original languageEnglish (US)
Pages (from-to)600-610
Number of pages11
JournalInternational Journal of Cancer
Volume140
Issue number3
DOIs
StatePublished - Feb 1 2017

Keywords

  • circulating inflammation markers
  • endometrial cancer
  • nested case-contro
  • prediagnostic

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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