lisinopril and Kidney-Neoplasms

Topics: Adrenal Cortex Hormones; Amlodipine; Angioedema; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Antineoplastic Agents; Calcium Channel Blockers; Carcinoma, Renal Cell; Drug Administration Schedule; Drug Interactions; Everolimus; Female; Humans; Kidney Neoplasms; Lisinopril; Middle Aged; Sirolimus; TOR Serine-Threonine Kinases

Topics: Angiogenesis Inhibitors; Antihypertensive Agents; Carcinoma, Renal Cell; Combined Modality Therapy; Humans; Hypertension; Indoles; Kidney Neoplasms; Lisinopril; Male; Middle Aged; Nephrectomy; Pyrroles; Sunitinib; Treatment Outcome; Withholding Treatment

Clinical and experimental studies suggest cross-talk between lipid metabolism and the renin-angiotensin system (RAS) in atherogenesis. The aim of this study was to explore interactions between these two systems in mediating cancer risk in type 2 diabetes.. A prospective cohort of 4,160 Chinese patients with type 2 diabetes, free of cancer at enrollment, were analyzed using Cox models. Interaction of RAS inhibitors (angiotensin I-converting enzyme inhibitors or angiotensin II receptor blockers) and statins was estimated using relative excess risk due to interaction (RERI), attributable proportion due to interaction (AP), and synergy index (S). RERI > 0, AP > 0, or S > 1 indicates additive interaction between the two classes of drugs. Molecular mechanisms underlying these interactions were explored using a uninephrectomy (UNX) rat model with renal carcinogenesis.. During 21,992 person-years of follow-up, 190 patients developed cancer. Use of RAS inhibitors and statins in isolation or combination during follow-up was associated with reduced risk of cancer after adjustment for covariates. The multivariable RERI and AP for the additive interaction between these drug classes for cancer were significant (0.53 [95% CI 0.20-0.87] and 2.65 [0.38-4.91], respectively). In the UNX rat model, inhibition of the RAS prevented renal cell carcinoma by normalizing hydroxymethylglutaryl-CoA reductase (HMGCR) expression and the insulin-like growth factor-1 (IGF-1) signaling pathway.. Combined use of RAS inhibitors and statins may act synergistically to reduce cancer risk, possibly via HMGCR and IGF-1 signaling pathways in high-risk conditions such as type 2 diabetes.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Carcinoma, Renal Cell; Cohort Studies; Diabetes Mellitus, Type 2; Disease Models, Animal; Hong Kong; Humans; Inpatients; Insulin-Like Growth Factor I; Kidney Function Tests; Kidney Neoplasms; Lipids; Lisinopril; Neoplasms; Outpatients; Rats; Rats, Sprague-Dawley; Registries; Renin-Angiotensin System; Risk Factors