Oxylipins Correlate with Quality of Life in Women Taking Aromatase Inhibitors for Breast Cancer

Abstract

We aimed to evaluate post-treatment inflammatory biomarkers, namely C-reactive protein (CRP), interleukin-6 (IL6), monocytes chemoattractant protein-1 (MCP1), leptin and adiponectin, in relation to overall survival (OS) in stage II-III colorectal cancer (CRC) patients. Methods: Participants were incident, invasive CRC cases who were 22-74 years of age, diagnosed between 1997-2008 from the populationbased Seattle Colon Cancer Family Registry. We included stage II-III cases who were at the greatest risk for disease progression. Further restriction to 308 participants with a blood draw 1-3 years after diagnosis was made to preclude acute treatment effects. We measured concentrations of all five markers in EDTA-plasma samples using the Meso Scale Discovery immunoassays. Biomarker levels were logtransformed to ensure normality. We also divided patients into sexspecific quartiles for each marker to test for a dose-effect of a biomarker on disease progression. Mortality and cause of death were assessed through linkage to the National Death Index. We used Cox proportional hazard regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of post-treatment inflammatory markers with OS. HRs were adjusted for potential confounders selected a priori, including age at blood draw, sex, body mass index, plasma storage time, the time between diagnosis and blood draw, and stage at diagnosis. Results: Elevated CRP levels were associated with poorer OS (HR ¼ 1.32 per unit increase of log-CRP, 95% CI ¼ 1.13-1.55). For circulating IL6, a dose-response relationship with survival was evident: compared with the lowest quartile of IL6, the 2nd, 3rd and 4th quartiles were significantly associated with OS, with HRs (95% CIs) of 2.72 (1.42-5.21), 4.23 (2.24-7.99), and 6.80 (3.56-12.96) respectively (p for trend < 0.0001). For MCP1, we observed a 2-fold increase in the risk of overall mortality per unit increase in log-MCP1 (HR ¼ 2.17, 95% CI ¼ 1.39-3.39). Circulating levels of leptin and adiponectin were not significantly associated with OS. Conclusions: Circulating inflammatory markers, specifically CRP, IL6, and MCP1, are prognostic markers in stage II/III CRC patients and should be considered for incorporation into studies of CRC outcomes.