Abstract 22: Prediagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: Preliminary results.
Authors: Trabert Britton , Pinto Ligia , Hartge Patricia , Kemp Troy , Black Amanda , Sherman Mark E. , Brinton Louise A. , Pfeiffer Ruth , Chaturvedi Anil , Hildesheim Allan , Wentzensen Nicolas 
Published: August 2013

Abstract
Background: Ovarian cancer is linked to pro-inflammatory mechanisms through its association with increased lifetime number of ovulations, pelvic inflammatory disease, endometriosis, and exposure to talc and asbestos. Exposures that directly reduce inflammation, such as non-steroidal anti-inflammatory drugs and factors that may reduce exposure to irritants, including tubal ligation and hysterectomy, have been shown to reduce ovarian cancer risk. However, limited data are available linking ovarian cancer to measurements of circulating inflammatory markers.
Methods: To evaluate whether circulating levels of cytokines and other immune markers are associated with ovarian cancer risk, we conducted a nested case-control study within the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial. Four Luminex based multi-plex panels were used to measure circulating levels of 60 inflammation-related biomarkers in all 150 incident ovarian cancer cases with pre-diagnostic serum samples available and 149 controls matched on age at baseline, race, date and time of day of sample collection. Serum samples were collected between 2 and 13 years before cancer diagnosis. We limited analysis to the 24 markers with at least 67% of values above the lower limit of detection and categorized the markers based on the tertile (n=2 markers) or quartile (n=22 markers) distribution in controls. Coefficients of variation for these 24 markers ranged from 1% to 13%. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression in unadjusted models and with further adjustment for parity, oral contraceptive use, menopausal hormone therapy use, cigarette smoking and body mass index.
Results: In preliminary analyses, elevated serum levels of IL-8 were associated with increased risk of ovarian cancer [Q4 vs. Q1: adjusted OR 2.62 95% CI (1.15-5.95)]. Elevated serum levels of CRP and TNF-alpha were marginally associated with an increased risk [CRP Q4 vs. Q1: 2.11 (0.97-4.59); TNF-alpha Q4 vs. Q1: 2.27 (0.98-5.28)]. In analyses restricted to serous ovarian cancer, the associations with IL-8 and CRP were strengthened [IL-8 Q4 vs. Q1: 3.47 (1.04-11.55); CRP Q4 vs. Q1: 5.62 (1.54-20.56)]. Elevated IL-8, CRP and TNF-alpha levels were statistically significantly related to increased ovarian cancer risk in analysis restricted to specimens collected at least 5 years before diagnosis.
Conclusions: Our preliminary results suggest a positive association between IL-8, CRP and TNF-alpha and increased ovarian cancer risk. Our findings confirm an increased risk of ovarian cancer reported for CRP. Associations between IL-8 and TNF-alpha with ovarian cancer risk have not been previously reported, but both markers have been shown to be involved in ovarian function, specifically follicle rupture and repair, and are detectable in tumor tissue from ovarian cancer patients. These findings suggest that increased inflammation is etiologically important in ovarian carcinogenesis, and argue for additional research to confirm and extend these findings.
Citation Format: Britton Trabert, Ligia Pinto, Patricia Hartge, Troy Kemp, Amanda Black, Mark E. Sherman, Louise A. Brinton, Ruth Pfeiffer, Anil Chaturvedi, Allan Hildesheim, Nicolas Wentzensen. Prediagnostic serum levels of inflammation markers and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial: Preliminary results. [abstract]. In: Proceedings of the AACR Special Conference on Post-GWAS Horizons in Molecular Epidemiology: Digging Deeper into the Environment; 2012 Nov 11-14; Hollywood, FL. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2012;21(11 Suppl):Abstract nr 22.