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J. Clin. Med. 2018, 7(8), 197; https://doi.org/10.3390/jcm7080197

Anti-Hypertensive Medication Use, Soluble Receptor for Glycation End Products and Risk of Pancreatic Cancer in the Women’s Health Initiative Study

1
Section of Epidemiology and Population Sciences, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
2
Section of Gastroenterology and Hepatology, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
3
Center for Innovations in Quality, Effectiveness and Safety (IQuESt), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA
4
Section of Health Services Research, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
5
Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA
6
Texas Medical Center Digestive Disease Center, Houston, TX 77030, USA
7
Dan L. Duncan Cancer Center at Baylor College of Medicine, Houston, TX 77030, USA
8
Center for Translational Research on Inflammatory Diseases (CTRID), Michael E. DeBakey VA Medical Center, Houston, TX 77030, USA
9
Departments of Epidemiology and Medicine, Gillings School of Global Public Health and School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
10
Geriatric Research Education and Clinical Center (GRECC), Puget Sound Department of Veterans Affairs Medical Center, Seattle, WA 98108, USA
11
Section of Endocrinology, Department of Medicine, University of Washington, Seattle, WA 98195, USA
*
Author to whom correspondence should be addressed.
Received: 17 July 2018 / Accepted: 26 July 2018 / Published: 2 August 2018
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Abstract

Pancreatic cancer is the fourth leading cause of cancer death. Soluble receptor for glycation end products (sRAGE), which is modulated by anti-hypertensive (HT) medications, has been inversely associated with pancreatic cancer. However, the association between commonly used anti-HT medications and risk of pancreatic cancer is unknown. A total of 145,551 postmenopausal women from the Women Health Initiative (WHI) Study were included in analysis. Use of angiotensin converting enzyme inhibitors (ACEi), β-blockers, calcium channel blockers (CCBs) and diuretics was ascertained at baseline (1993–1998). Baseline sRAGE levels were measured among a subset of 2104 participants using an immunoassay. Multivariable Cox proportional hazard regression model was performed to estimate hazard ratios (HRs) and its 95% confidence intervals (CIs) for pancreatic cancer in association with anti-HT medications. Increased risk of pancreatic cancer was found among users of short-acting CCB (HR = 1.66, 95% CI: 1.20–2.28) and long-term (≥3 years) users of short-acting CCB (HR = 2.07, 95% CI: 1.42–3.02) compared to users of other anti-HT medications. Average sRAGE levels were lower in short-acting CCB users than users of other anti-HT medications (1173 versus 1454 pg/mL, p = 0.038). Non-statistically significant reduced risk of pancreatic cancer was found among users of β-blockers (HR = 0.80, 95% CI: 0.60–1.07). Average sRAGE levels were higher in β-blockers users than users of other anti-HT medications (1692 versus 1454 pg/mL, p > 0.05). Future studies are warranted to confirm these findings and elucidate potential mechanisms by which anti-HT medications influence development of pancreatic cancer. View Full-Text
Keywords: pancreatic neoplasm; pharmacoepidemiology; hypertension; calcium channel blocker; inflammation; risk factor; sRAGE pancreatic neoplasm; pharmacoepidemiology; hypertension; calcium channel blocker; inflammation; risk factor; sRAGE
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Wang, Z.; White, D.L.; Hoogeveen, R.; Chen, L.; Whitsel, E.A.; Richardson, P.A.; Virani, S.S.; Garcia, J.M.; El-Serag, H.B.; Jiao, L. Anti-Hypertensive Medication Use, Soluble Receptor for Glycation End Products and Risk of Pancreatic Cancer in the Women’s Health Initiative Study. J. Clin. Med. 2018, 7, 197.

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