Circulating Inflammation Markers and Risk of Epithelial Ovarian Cancer

Abstract

BACKGROUND: Factors contributing to chronic inflammation appear to be associated with increased risk of ovarian cancer. The purpose of this study was to assess the association between circulating levels of inflammation mediators and subsequent risk of ovarian cancer. METHODS: We conducted a case-control study of 230 cases and 432 individually matched controls nested within three prospective cohorts to evaluate the association of prediagnostic circulating levels of inflammation-related biomarkers (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12p40, IL-12p70, IL-13, TNFα, IL-1Ra, sIL-1RII, sIL-2Ra, sIL-4R, sIL-6R, sTNF-R1, and sTNF-R2) measured using Luminex xMap technology with risk of ovarian cancer. RESULTS: We observed a trend across quartiles for IL-2 (OR(Q4 vs. Q1): 1.57, 95% CI: 0.98-2.52, P = 0.07), IL-4 (OR(Q4 vs. Q1): 1.50, 95% CI: 0.95-2.38, P = 0.06), IL-6 (OR(Q4 vs. Q1): 1.63, 95% CI: 1.03-2.58, P = 0.03), IL-12p40 (OR(Q4 vs. Q1): 1.60, 95% CI: 1.02-2.51, P = 0.06), and IL-13 (OR(Q4 vs. Q1): 1.42, 95% CI: 0.90-2.26, P = 0.11). Trends were also observed when cytokines were modeled on the continuous scale for IL-4 (P trend = 0.01), IL-6 (P trend = 0.01), IL-12p40 (P trend = 0.01), and IL-13 (P trend = 0.04). ORs were not materially different after excluding cases diagnosed less than 5 years after blood donation or when limited to serous tumors. CONCLUSIONS AND IMPACT: This study provides the first direct evidence that multiple inflammation markers, specifically IL-2, IL-4, IL-6, IL-12, and IL-13, may be associated with risk of epithelial ovarian cancer, and adds to the evidence that inflammation is involved in the development of this disease.