Inflammatory markers of CRP, IL6, TNFα, and Soluble TNFR2 and the risk of ovarian cancer: A meta-analysis of prospective studies

Background: There has been growing evidence showing that inflammatory markers play an important role in the development of ovarian cancer. We conducted a meta-analysis on the associations between circulating levels of C-reactive protein (CRP), interleukin 6 (IL6), tumor necrosis factor α (TNFα), and soluble TNFα receptor 2 (TNFR2), and the risk of ovarian cancer. Methods: A systematic search of PubMed and EMBASE up until January 19, 2016 was conducted to retrieve prospective studies. The summary risk estimates were pooled using random-effects models. The dose-response relationship was assessed using generalized least-squares trend estimation. Results: Seven nested case-control studies and one prospective cohort study were included in the review. For circulating CRP, women in the highest category had a significantly increased risk of ovarian cancer than women in the lowest category, with no significant between-study heterogeneity [pooled relative risk (RR)=1.91; 95% confidence intervals (CI) 1.51-2.40; P < 0.001; I² = 0.0%]. Influence analyses further supported this positive association. A positive dose-response relationship was also observed (pooled RR =1.15;95%CI, 1.03-1.30 per 5mg/L of CRP). Publication bias was found. However, the association persisted after correction using the trim-and-fill method. No significant association was observed for circulating IL6, TNFα, and soluble TNFR2. Conclusion: This meta-analysis provides evidence that elevated levels of CRP, but not circulating IL6, TNFα, or soluble TNFR2, are significantly associated with an increased risk of ovarian cancer. Impact: These results suggest that circulating CRP may play a role in the etiology of ovarian cancer.