A prospective study of circulating C-reactive protein, interleukin-6, and tumor necrosis factor α receptor 2 levels and risk of ovarian cancer

Am J Epidemiol. 2013 Oct 15;178(8):1256-64. doi: 10.1093/aje/kwt098. Epub 2013 Aug 21.


Chronic inflammation may play a role in ovarian carcinogenesis. We examined associations between 3 plasma biomarkers of inflammation-C-reactive protein (CRP), interleukin 6, and tumor necrosis factor α receptor 2-and risk of invasive epithelial ovarian cancer in prospectively collected samples from the Nurses' Health Study (NHS; 1989-2010), Nurses' Health Study II (NHS II; 1996-2009), and the Women's Health Study (WHS; 1992-2011) and performed a meta-analysis including data from previous publications. Associations with ovarian cancer risk were calculated using logistic regression (NHS/NHS II; n = 217 cases) or Cox proportional hazards regression (WHS; n = 159 cases). Study-specific results were combined using random-effects meta-analysis. In the NHS/NHS II and WHS, we observed a 53% increased risk of invasive ovarian cancer when comparing women in the fourth quartile of CRP with women in the first quartile (95% confidence interval (CI): 1.05, 2.23). A CRP level of >10 mg/L versus a level of ≤1 mg/L was associated with a 2.16-fold increased risk (95% CI: 1.23, 3.78). In a meta-analysis of published studies, women in the third tertile of CRP had a 35% increased risk (95% CI: 1.10, 1.67) compared with women in the first tertile. There were no significant associations between interleukin 6 or tumor necrosis factor α receptor 2 and risk in the NHS/NHS II. Our results support the hypothesis that higher levels of circulating CRP are associated with increased risk of ovarian cancer, indicating that the role of inflammation in ovarian cancer requires further elucidation.

Keywords: C-reactive protein; interleukin 6; ovarian cancer; tumor necrosis factor α receptor 2.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Aged
  • C-Reactive Protein / analysis*
  • Female
  • Humans
  • Interleukin-6 / blood*
  • Middle Aged
  • Ovarian Neoplasms / blood*
  • Prospective Studies
  • Receptors, Tumor Necrosis Factor, Type II / blood*
  • Risk
  • Tumor Necrosis Factor-alpha / blood


  • Interleukin-6
  • Receptors, Tumor Necrosis Factor, Type II
  • Tumor Necrosis Factor-alpha
  • C-Reactive Protein