ASPO Abstracts
Pre-diagnostic serum levels of arachidonic acid and linoleic acid metabolites and risk of ovarian cancer in the Prostate, Lung, Colorectal and Ovarian Cancer (PLCO) Screening Trial.
Category: Inflammation & Cancer, Molecular Epidemiology & Environment
Conference Year: 2018
Abstract Body:
Introduction Inflammation is a strong risk factor for ovarian cancer but the mechanism is not well understood. Several studies demonstrate that inflammation related to ovulation, endometriosis, and pelvic inflammatory disease is associated with increased risk for ovarian cancer. Evidence also suggests that anti-inflammatory drugs, including aspirin, decrease risk. Aspirin and other NSAIDs block the synthesis of prostanoids by inhibiting the cyclooxygenase (COX) enzyme. Studies of inflammatory mediators, lipid molecules such as arachidonic acid (AA) and linoleic acid (LA) metabolites, and subsequent development of ovarian cancer are essential to uncovering mechanism. Method We conducted a study nested within in the PLCO Cancer Screening Trial to measure pre-diagnostic serum levels of 32 AA/LA metabolites, representing 3 different pathways [COX, cytochrome P450 (P450), and lipoxygenase (LOX)]. We measured levels in 157 women who eventually developed ovarian cancer and 157 matched controls. We calculated odds ratios (OR) and 95% confidence intervals (CI) for the association between metabolite levels and risk of ovarian cancer, overall and by histologic subtype (serous/non-serous), using logistic regression and adjusted for matching factors and potential confounders. Result Five of the 32 AA/LA metabolites evaluated were positively associated with ovarian cancer risk: 12-13-DHOME [Tertile 3 vs. 1: OR 2.44 (95% CI 1.27- 4.70), p-trend 0.01], 13-HODE [2.45 (1.30- 4.58), 0.01], 9-HODE [1.95 (1.05-3.63), 0.03], 9,12,13-THOME [2.23 (1.19-4.16), 0.01], 8-HETE [1.83 (1.01-3.26), 0.04]. In analyses by subtype, heterogeneity was observed for 2 metabolites: 12-13-EpOME [serous: 1.95 (0.90-4.21)], non-serous: 0.81 (0.39-1.70), p-het 0.02] and 8-HETE [2.48 (1.16-5.30), 1.16 (0.57-2.39), p-het 0.01], suggesting increased serous tumor risk. Increased levels of five fatty acid metabolites (12-13-DHOME, 13-HODE, 9-HODE, 9,12,13-THOME, and 8-HETE) are associated with increased ovarian cancer risk. All five metabolites are derived from either LA (12-13-DHOME, 13-HODE, 9,12,13-THOME, 9-HODE) or AA (8-HETE) via metabolism through the LOX/ P450 pathway. Future studies replicating these findings and/or evaluating LOX/P450 pathway metabolism and ovarian carcinogenesis are warranted.
Keywords: Arachidonic acid, Linoleic acid, Eicosanoids, ovarian cancer