title: Renin angiotensin system inhibitors may attenuate low LDL cholesterol-related cancer risk in type 2 diabetes.
abstract: BACKGROUND
  In type 2 diabetes (T2D), copresence of low-density lipoprotein cholesterol (LDL-C) < 2.8 mmol/L with triglyceride < 1.7 mmol/L or with albuminuria synergistically increased cancer risk. We tested whether use of renin angiotensin system inhibitors attenuated the increased cancer risk associated with these two risk subphenotypes.
  
  
  METHODS
  A prospective cohort of 4307 patients with T2D enrolled from December 1996 to January 2005 was analysed using a new user cohort design. Cox model analysis was used to obtain hazard ratios and 95% confidence intervals. The study measured additive interactions between nonuse of renin angiotensin system inhibitors and low LDL-C plus low triglyceride or albuminuria for the risk of cancer. A positive interaction suggests a specific drug effect on the low LDL-C-related cancer risk.
  
  
  RESULTS
  During 18 769 person years of follow-up (median follow-up years: 4.44), 4.48% (n = 193) of patients developed cancer. Use of renin angiotensin system inhibitors was associated with reduced cancer risk among patients with copresence of low LDL-C plus low triglyceride or low LDL-C plus albuminuria but not in patients without these subphenotypes. In multivariable analysis, renin angiotensin system inhibitor usage attenuated the hazard ratio of copresence of low LDL-C plus low triglyceride versus lack of this subphenotype for cancer from 2.08 (95% CI: 1.25-3.47) to 1.13 (0.61-2.11) with significant additive interaction (p = 0.0225). Similarly, RAS inhibitor usage attenuated the hazard ratio of copresence of low LDL-C plus albuminuria versus lack of this subphenotype for cancer from 1.99 (95% CI: 1.12-3.56) to 0.82 (0.43-1.54) with significant additive interaction (p = 0.0009).
  
  
  CONCLUSIONS
  In T2D, renin angiotensin system inhibitor usage may specifically attenuate the low LDL-C-related cancer risk.
authors.forename: Xilin
authors.initials: X
authors.lastname: Yang
authors.forename: Ronald C W
authors.initials: RC
authors.lastname: Ma
authors.forename: Wing Yee
authors.initials: WY
authors.lastname: So
authors.forename: Ying
authors.initials: Y
authors.lastname: Wang
authors.forename: Alice P S
authors.initials: AP
authors.lastname: Kong
authors.forename: Risa
authors.initials: R
authors.lastname: Ozaki
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.forename: Juliana C N
authors.initials: JC
authors.lastname: Chan
mesh_terms: D000368:Aged; D000419:Albuminuria / Q000150:complications; D057911:Angiotensin Receptor Antagonists / Q000627:therapeutic use*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D008078:Cholesterol, LDL / Q000097:blood; D015331:Cohort Studies; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000517:prevention & control*; D011446:Prospective Studies; D012042:Registries; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012306:Risk; D014280:Triglycerides / Q000097:blood
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides
keywords: RAS inhibitors; additive interaction; albuminuria; cancer; low LDL cholesterol; low triglyceride; type 2 diabetes