Renin-Angiotensin-Aldosterone System Inhibitors and Development of Gynecologic Cancers: A 23 Million Individual...

The chronic receipt of renin-angiotensin-aldosterone system (RAAS) inhibitors including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) have been assumed to be associated with a significant decrease in overall gynecologic cancer risks. This study aimed to investigate the associations of long-term RAAS inhibitors use with gynecologic cancer risks. A large population-based case-control study was conducted from claim databases of Taiwan's Health and Welfare Data Science Center (2000-2016) and linked with Taiwan Cancer Registry (1979-2016). Each eligible case was matched with four controls using propensity matching score method for age, sex, month, and year of diagnosis. We applied conditional logistic regression with 95% confidence intervals to identify the associations of RAAS inhibitors use with gynecologic cancer risks. The statistical significance threshold was p < 0.05. A total of 97,736 gynecologic cancer cases were identified and matched with 390,944 controls. The adjusted odds ratio for RAAS inhibitors use and overall gynecologic cancer was 0.87 (95% CI: 0.85-0.89). Cervical cancer risk was found to be significantly decreased in the groups aged 20-39 years (aOR: 0.70, 95% CI: 0.58-0.85), 40-64 years (aOR: 0.77, 95% CI: 0.74-0.81), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.91), and overall (aOR: 0.81, 95% CI: 0.79-0.84). Ovarian cancer risk was significantly lower in the groups aged 40-64 years (aOR: 0.76, 95% CI: 0.69-0.82), ≥65 years (aOR: 0.83, 95% CI: 0.75-092), and overall (aOR: 0.79, 95% CI: 0.74-0.84). However, a significantly increased endometrial cancer risk was observed in users aged 20-39 years (aOR: 2.54, 95% CI: 1.79-3.61), 40-64 years (aOR: 1.08, 95% CI: 1.02-1.14), and overall (aOR: 1.06, 95% CI: 1.01-1.11). There were significantly reduced risks of gynecologic cancers with ACEIs users in the groups aged 40-64 years (aOR: 0.88, 95% CI: 0.84-0.91), ≥65 years (aOR: 0.87, 95% CI: 0.83-0.90), and overall (aOR: 0.88, 95% CI: 0.85-0.80), and ARBs users aged 40-64 years (aOR: 0.91, 95% CI: 0.86-0.95). Our case-control study demonstrated that RAAS inhibitors use was associated with a significant decrease in overall gynecologic cancer risks. RAAS inhibitors exposure had lower associations with cervical and ovarian cancer risks, and increased endometrial cancer risk. ACEIs/ARBs use was found to have a preventive effect against gynecologic cancers. Future clinical research is needed to establish causality.