Abstract B21: C-reactive protein and ovarian cancer risk in the Ovarian Cancer Cohort Consortium
Authors: Trabert Britton , Fortner Renee , Poole Elizabeth , Wentzensen Nicolas , Tworoger Shelley 
Published: August 2018

Abstract
Background: C-reactive protein (CRP), a general marker of inflammation, has been consistently associated with increased ovarian cancer risk. However, few studies have had the ability to evaluate differences in association by ovarian tumor subtype. Thus, we leveraged previously measured CRP levels in prediagnostic specimens from 6 studies in the Ovarian Cancer Cohort Consortium (OC3).
Methods: We pooled data on CRP and ovarian cancer risk among nested case-control studies conducted in CLUEII, EPIC, NHS, NHSII, NYUWHS, and PLCO; invasive ovarian cancer cases were matched to one or two controls on age, menopausal status, hormone therapy (HT) use, and fasting status. Due to variability in CRP distributions across studies in part due to different assays, we regressed CRP levels on study (with EPIC as the reference), adjusting for predictors of CRP, including age, menopause/HT status, fasting status, BMI, aspirin use, and smoking. Levels for each study (except EPIC) were recalibrated based on the beta coefficient for that study. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for natural log-transformed CRP (continuous), quartiles (based on control distributions) and clinical cutpoints (&lt;1, 1-&lt;10, ≥10mg/L) using conditional logistic regression, which implicitly accounts for matching factors. We examined associations for all invasive cancer and by histotype (serous [n=740], endometrioid [n=109], mucinous [n=69], clear cell [n=47]). Primary analyses (model 1) adjusted for reproductive risk factors (oral contraceptive use, number of pregnancies, and tubal ligation); model 2 additionally adjusted for known predictors of CRP, including BMI, smoking, and aspirin use, that also may be related to ovarian cancer risk.
Results: There was a marginally significant linear association between CRP and total invasive ovarian cancer risk among 1,135 cases and 2,124 controls (p-trend=0.05), which was slightly attenuated when adjusting for BMI, smoking, and aspirin use (p-trend=0.08). The model 1 OR (95% CI) was 1.24 (0.99-1.54) comparing the top to bottom quartile and 1.90 (1.28-2.81) for ≥10 to &lt;1 mg/L. The corresponding OR (95% CI) for model 2 was 1.21 (0.96-1.53) and 1.86 (1.24-2.79), respectively. Results were generally similar across histotypes with the strongest associations comparing CRP levels ≥10 vs. &lt;1mg/L, although no associations reached statistical significance. Interestingly, the impact of adjusting for BMI, smoking, and aspirin differed across subtypes. For example, the OR (95% CI) comparing the top versus bottom quartile for serous tumors increased from 1.25 (0.95-1.65) in model 1 (reproductive factors) to 1.31 (0.97-1.75) in model 2 (reproductive factors and predictors of CRP). Conversely, the association was largely attenuated for endometrioid tumors when adjusting for predictors of CRP (model 1: OR=1.37 [0.72-2.58]; model 2: OR=1.06 [0.52-2.18]).
Conclusion: Our results confirm that CRP, particularly very high levels, is positively associated with risk of ovarian cancer. The association for serous tumors appeared to be independent of reproductive exposures and other factors that are associated with CRP and ovarian cancer; however, the relationship observed for endometrioid tumors was largely explained by BMI. Given that fewer risk factors have been identified for serous tumors, our work supports further exploration of inflammation and immunity in the etiology of this histotype. Further analyses will explore associations by other tumor factors (e.g., grade) and participant characteristics (e.g., menopausal status).
Citation Format: Britton Trabert, Renee Fortner, Elizabeth Poole, Nicolas Wentzensen, Shelley Tworoger. C-reactive protein and ovarian cancer risk in the Ovarian Cancer Cohort Consortium. [abstract]. In: Proceedings of the AACR Conference: Addressing Critical Questions in Ovarian Cancer Research and Treatment; Oct 1-4, 2017; Pittsburgh, PA. Philadelphia (PA): AACR; Clin Cancer Res 2018;24(15_Suppl):Abstract nr B21.