Abstract 4946: The association between antihypertensive medication, sRAGE, and risk of pancreatic cancer: Results from the Women's Health Initiative Study

Abstract

Abstract Background: Pancreatic cancer is the 4th leading cause of cancer-related death in the United States. With its anti-inflammatory property, soluble receptor for advanced glycation end-product (sRAGE) has been associated with lower risk of pancreatic cancer. Antihypertensive medications were shown to modulate sRAGE levels and AGE/RAGE signaling pathway. However, few large-scale population-based studies have evaluated the associations between antihypertensive medications and risk of pancreatic cancer.Methods: A total of 145,553 postmenopausal women aged 50 to 79 years with no prevalent cancer from Women's Health Initiative (WHI) were included in our prospective cohort study with a mean follow-up of 13.8 years. Medication data including product and generic name, duration of use, and dosage form were collected at baseline recruitment (1993-98). We interrogated four antihypertensive drugs including β-blockers, diuretics, angiotensin converting enzyme inhibitors (ACEi) and calcium channel blockers (CCBs). Serum levels of sRAGE were measured in a subset of 842 study participants using immunoassay. Cox proportional hazard regression model was performed to obtain hazard ratio (HR) and its 95% confidence interval (CI) for each antihypertensive medication use and its duration of use in association with risk of pancreatic cancer. We additionally used Fine and Grey method to account for competing risk of nonpancreatic cancer deaths.Results: By August 29, 2014, a total of 841 incident pancreatic cancer cases were ascertained through annual self-administered questionnaires and confirmed by central adjudication. A 33% increased risk of pancreatic cancer was found among ever users of CCBs compared with never users (HR=1.33, 95% CI: 1.06-1.67) after adjusting for age, ethnicity, BMI, smoking status, diabetes history, use of β-blockers, ACEi or diuretics. The association remained after accounting for competing risks (HR=1.36, 95% CI: 1.30-1.42). Compared with never users of CCBs, long-term users (>3 years) had a 48% higher risk of pancreatic cancer (HR=1.48, 95% CI: 1.13-1.95, P trend = 0.005) and the association slightly attenuated but remained significant in the competing risk model (HR=1.35, 95% CI: 1.28-1.42, P trend < 0.001). The average serum sRAGE level was lower in CCBs ever users than CCBs never users (1,284 pg/mL versus 1,457 pg/mL, P = 0.011). Other antihypertensive medication use including β-blockers, diuretics, and ACEi were not associated with risk of pancreatic cancer.Conclusions: We found a positive association between CCB use and risk of incident pancreatic cancer in postmenopausal women. The inverse association between sRAGE level and CCBs use may help explain this association. Future studies are warranted to confirm these findings and further elucidate potential mechanisms by which CCBs may influence development of pancreatic cancer. Citation Format: Zhensheng Wang, Donna White, Liang Chen, Peter Richardson, Hashem B. El-Serag, Li Jiao. The association between antihypertensive medication, sRAGE, and risk of pancreatic cancer: Results from the Women's Health Initiative Study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4946.