Inflammatory Markers and Risk of Epithelial Ovarian Cancer by Tumor Subtypes: The EPIC Cohort.
Ose J., Schock H., Tjønneland A., Hansen L., Overvad K., Dossus L., Clavel-Chapelon F., Baglietto L., Boeing H., Trichopolou A., Benetou V., Lagiou P., Masala G., Tagliabue G., Tumino R., Sacerdote C., Mattiello A., Bueno-de-Mesquita HB., Peeters PH., Onland-Moret NC., Weiderpass E., Gram IT., Sánchez S., Obon-Santacana M., Sànchez-Pérez MJ., Larrañaga N., Castaño JM., Ardanaz E., Brändstedt J., Lundin E., Idahl A., Travis RC., Khaw KT., Rinaldi S., Romieu I., Merritt MA., Gunter MJ., Riboli E., Kaaks R., Fortner RT.
BACKGROUND: Evidence suggests an etiologic role for inflammation in ovarian carcinogenesis and heterogeneity between tumor subtypes and anthropometric indices. Prospective studies on circulating inflammatory markers and epithelial invasive ovarian cancer (EOC) have predominantly investigated overall risk; data characterizing risk by tumor characteristics (histology, grade, stage, dualistic model of ovarian carcinogenesis) and anthropometric indices are sparse. METHODS: We conducted a nested case-control study in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort to evaluate C-reactive protein (CRP), IL6, and EOC risk by tumor characteristics. A total of 754 eligible EOC cases were identified; two controls (n = 1,497) were matched per case. We used multivariable conditional logistic regression to assess associations. RESULTS: CRP and IL6 were not associated with overall EOC risk. However, consistent with prior research, CRP >10 versus CRP ≤1 mg/L was associated with higher overall EOC risk [OR, 1.67 (1.03-2.70)]. We did not observe significant associations or heterogeneity in analyses by tumor characteristics. In analyses stratified by waist circumference, inflammatory markers were associated with higher risk among women with higher waist circumference; no association was observed for women with normal waist circumference [e.g., IL6: waist ≤80: ORlog2, 0.97 (0.81-1.16); waist >88: ORlog2, 1.78 (1.28-2.48), Pheterogeneity ≤ 0.01]. CONCLUSIONS: Our data suggest that high CRP is associated with increased risk of overall EOC, and that IL6 and CRP may be associated with EOC risk among women with higher adiposity. IMPACT: Our data add to global evidence that ovarian carcinogenesis may be promoted by an inflammatory milieu.