Abstract LB-382: A prospective study of soluble receptor for advanced glycation end products and adiponectin and pancreatic cancer in postmenopausal women

Abstract

Abstract Obesity is a recognized pancreatic cancer risk factor. Obesity-associated chronic inflammation and insulin resistance as well as western diet are associated with increased circulating levels of advanced glycation end products (AGEs) levels. When AGEs bind to their receptor (RAGE) on adipocytes, an inflammatory cascade is triggered and dysregulation of adipokines can occur. Soluble RAGE (sRAGE) mitigates this negative effect by acting as a decoy receptor for AGEs. In a nested case-control study in the prospective Women's Health Initiative study, we assessed the association between baseline levels of sRAGE and adiponectin and pancreatic cancer risk in post-menopausal women. Medical, lifestyle, diet data, anthropometric measurements and fasting blood were collected at baseline (1993-98). Serum sRAGE and adiponectin levels were immunoassay measured. With an average follow-up 14 years (thru 8/2013), we identified 494 incident cases with pancreatic cancer. Two controls were matched to each case by age, ethnicity, trial assignment and blood draw time (± 6 mos.). Multivariable conditional logistic regression analysis was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for associations between sRAGE and adiponectin levels (quartile, Q) and pancreatic cancer after adjusting for waist-hip-ratio, diabetes, and dietary intake of alcohol, protein, saturated fat and carbohydrates. A total of 7.6% cases and 6.3% controls were current smokers. sRAGE was correlated with adiponectin among controls(r = 0.17, P <0.001). Higher sRAGE levels were associated with reduced risk of pancreatic cancer (aOR = 0.71, 95% CI: 0.56-0.90, P = 0.004 with sRAGE assessed as a continuous variable; aOR (Q4 vs Q1) = 0.75, 95% CI: 0.54-1.06, with P = 0.02 for trend across quartiles). Adiponectin was not associated with pancreatic cancer risk when assessed as a continuous variable (aOR = 1.008, 95% CI: 0.98-1.02); however, women with highest adiponectin levels had reduced risk of pancreatic cancer (aOR Q4 vs Q1 = 0.73, 95% CI: 0.51-1.04, P = 0.06 for trend). Women with higher levels of both sRAGE and adiponectin (above their respective medians) had greatest risk reduction (aOR = 0.59, 95% CI: 0.42-0.82) compared with women with lower levels of both biomarkers(P for interaction = 0.15). Consistent with our prior work in Finnish male smokers, we found an inverse association between pre-diagnostic sRAGE and risk of incident pancreatic cancer. We also identified a potential effect modification of adiponectin by sRAGE in postmenopausal women. The role of the RAGE pathway in obesity-related pancreatic cancer needs further investigation. Citation Format: Donna L. White, Ron Hoogeveen, Kathryn Royse, Liang Chen, Lesley Tinker, Tom Rohan, Eric Whitsel, Hashem B. El-Serag, Li Jiao. A prospective study of soluble receptor for advanced glycation end products and adiponectin and pancreatic cancer in postmenopausal women. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr LB-382.