title: Pioglitazone Use and Risk of Bladder Cancer and Other Common Cancers in Persons With Diabetes.
abstract: OBJECTIVE
  Studies suggest pioglitazone use may increase risk of cancers.
  
  
  OBJECTIVE
  To examine whether pioglitazone use for diabetes is associated with risk of bladder and 10 additional cancers.
  
  
  METHODS
  Cohort and nested case-control analyses among persons with diabetes. A bladder cancer cohort followed 193,099 persons aged 40 years or older in 1997-2002 until December 2012; 464 case patients and 464 matched controls were surveyed about additional confounders. A cohort analysis of 10 additional cancers included 236,507 persons aged 40 years or older in 1997-2005 and followed until June 2012. Cohorts were from Kaiser Permanente Northern California.
  
  
  METHODS
  Ever use, duration, cumulative dose, and time since initiation of pioglitazone as time dependent.
  
  
  METHODS
  Incident cancer, including bladder, prostate, female breast, lung/bronchus, endometrial, colon, non-Hodgkin lymphoma, pancreas, kidney/renal pelvis, rectum, and melanoma.
  
  
  RESULTS
  Among 193,099 persons in the bladder cancer cohort, 34,181 (18%) received pioglitazone (median duration, 2.8 years; range, 0.2-13.2 years) and 1261 had incident bladder cancer. Crude incidences of bladder cancer in pioglitazone users and nonusers were 89.8 and 75.9 per 100,000 person-years, respectively. Ever use of pioglitazone was not associated with bladder cancer risk (adjusted hazard ratio [HR], 1.06; 95% CI, 0.89-1.26). Results were similar in case-control analyses (pioglitazone use: 19.6% among case patients and 17.5% among controls; adjusted odds ratio, 1.18; 95% CI, 0.78-1.80). In adjusted analyses, there was no association with 8 of the 10 additional cancers; ever use of pioglitazone was associated with increased risk of prostate cancer (HR, 1.13; 95% CI, 1.02-1.26) and pancreatic cancer (HR, 1.41; 95% CI, 1.16-1.71). Crude incidences of prostate and pancreatic cancer in pioglitazone users vs nonusers were 453.3 vs 449.3 and 81.1 vs 48.4 per 100,000 person-years, respectively. No clear patterns of risk for any cancer were observed for time since initiation, duration, or dose.
  
  
  CONCLUSIONS
  Pioglitazone use was not associated with a statistically significant increased risk of bladder cancer, although an increased risk, as previously observed, could not be excluded. The increased prostate and pancreatic cancer risks associated with ever use of pioglitazone merit further investigation to assess whether they are causal or are due to chance, residual confounding, or reverse causality.
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia2Department of Biostatistics and Epidemiology, University of Pennsylvania3Department of Medicine, University of Pennsylvania.
authors.forename: James D
authors.initials: JD
authors.lastname: Lewis
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Laurel A
authors.initials: LA
authors.lastname: Habel
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Charles P
authors.initials: CP
authors.lastname: Quesenberry
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia2Department of Biostatistics and Epidemiology, University of Pennsylvania5Rutgers Biomedical and Health Sciences, New Brunswick, New Jersey.
authors.forename: Brian L
authors.initials: BL
authors.lastname: Strom
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Tiffany
authors.initials: T
authors.lastname: Peng
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Monique M
authors.initials: MM
authors.lastname: Hedderson
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Samantha F
authors.initials: SF
authors.lastname: Ehrlich
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia2Department of Biostatistics and Epidemiology, University of Pennsylvania3Department of Medicine, University of Pennsylvania.
authors.forename: Ronac
authors.initials: R
authors.lastname: Mamtani
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia2Department of Biostatistics and Epidemiology, University of Pennsylvania.
authors.forename: Warren
authors.initials: W
authors.lastname: Bilker
authors.affiliation: Department of Medicine, University of Pennsylvania.
authors.forename: David J
authors.initials: DJ
authors.lastname: Vaughn
authors.affiliation: Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia.
authors.forename: Lisa
authors.initials: L
authors.lastname: Nessel
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Stephen K
authors.initials: SK
authors.lastname: Van Den Eeden
authors.affiliation: Division of Research, Kaiser Permanente Northern California, Oakland.
authors.forename: Assiamira
authors.initials: A
authors.lastname: Ferrara
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced; D010190:Pancreatic Neoplasms / Q000139:chemically induced*; D000077205:Pioglitazone; D011471:Prostatic Neoplasms / Q000139:chemically induced*; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced*
chemical_list: D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077205:Pioglitazone