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.

Highlights

  • Pancreatic cancer is the fourth leading cause of cancer-related death in the United States [1]

  • A recent meta-analysis of 70 clinical trials found no significant associations between angiotensin II receptor blockers (ARBs), angiotensin-converting enzyme inhibitor (ACEi), β-blockers, calcium-channel blockers (CCBs), or diuretics and overall risk of developing cancer [5]

  • We previously showed a significant inverse association between soluble receptor for advanced glycation end products and risk of incident pancreatic cancer [6,7]

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Summary

Introduction

Pancreatic cancer is the fourth leading cause of cancer-related death in the United States [1]. The incidence of pancreatic cancer is expected to rise in the aging population where hypertension is one of the most common comorbidities with an estimated prevalence of 65% among population aged over 60 in the U.S [3] It will be of potential public health significance to establish an association between commonly used medications and pancreatic cancer development [4]. We previously showed a significant inverse association between soluble receptor for advanced glycation end products (sRAGE) and risk of incident pancreatic cancer [6,7]. We examined the associations between the use of ACEi, β-blockers, CCBs and diuretics and risk of developing incident pancreatic cancer in a large prospective cohort. We explored the association between sRAGE levels and the anti-HT medication use in a subset of study participants for a mechanistic explanation

Study Population
Ascertainment of Medication Use
Ascertainment of Pancreatic Cancer
Data Collection
Measurement of sRAGE
Statistical Analysis
Baseline Characteristics of Participants
Anti-HT Medications and Risk of Pancreatic Cancer
Duration of CCB Use and Risk of Pancreatic Cancer
Conclusions
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