Key result
Combined use of RAS inhibitors and statins demonstrated a significant additive interaction for reducing cancer risk in patients with type 2 diabetes (RERI 0.53; 95% CI 0.20-0.87).
Why the study?
Does the combined use of RAS inhibitors and statins reduce cancer risk in patients with type 2 diabetes?
Cohort (n=4,160)
Does the combined use of RAS inhibitors and statins reduce cancer risk in patients with type 2 diabetes?
Combined use of RAS inhibitors and statins may act synergistically to reduce cancer risk in patients with type 2 diabetes.
May support synergy for cancer risk reduction in T2D; leaves open causality and requires randomized confirmation before practice change.
OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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Yang et al. (2009) conducted a cohort in Type 2 diabetes (n=4,160). Combined use of RAS inhibitors and statins vs. Use of RAS inhibitors or statins in isolation, or non-use was evaluated on Cancer (RERI 0.53, 95% CI 0.20-0.87). Combined use of RAS inhibitors and statins demonstrated a significant additive interaction for reducing cancer risk in patients with type 2 diabetes (RERI 0.53; 95% CI 0.20-0.87).
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