White blood cell count and renin–angiotensin system inhibitors for the risk of cancer in type 2 diabetes

High white blood cell (WBC) predicted cancer-associated mortality and renin–angiotensin system (RAS) inhibitors have immunomodulating effects. We hypothesize that RAS inhibitors may reduce cancer risk associated with high WBC in type 2 diabetes mellitus (T2DM). A prospective cohort of 4570 Chinese T2DM patients, free of cancer at enrolment, were analyzed. Biological interaction between WBC groups and use of RAS inhibitors 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 biological interaction. During 4.89 years of follow-up, 205 (4.49%) patients developed cancer. WBC ≥ 8.2 × 10 9 counts/L plus non-use of RAS inhibitors was associated with elevated cancer risks in multivariable models. The RERI and AP for interaction between WBC ≥ 8.2 × 10 9 counts/L and non-use of RAS inhibitors were, respectively, 1.26 (95% CI: 0.22–2.31) and 0.50 (0.23–0.78). In patients with WBC ≥ 8.2 × 10 9 counts/L, use of RAS inhibitors was associated with 64% (31–81%) cancer risk reduction in multivariable analysis. In T2DM, increased WBC predicts cancer while use of RAS inhibitors may reduce cancer risks associated with high WBC count.