Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes.
OBJECTIVE
Peroxisome proliferator-activated receptor gamma (PPARgamma) mediates cell cycle arrest and adipocyte differentiation; has tumor suppressor activity in liposarcoma, lung, and prostate cancers; and suppresses colonic polyp formation in adenomatous polyposis coli (APC)min/+ mice. To assess the influence of thiazolidinediones (TZDs), which are PPAR ligands used to treat diabetes mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical centers was conducted.


METHODS
Data on male patients 40 years and older diagnosed to have diabetes mellitus between 1997 and 2003 were obtained from the Veterans Integrated Services Network 16 (VISN 16) data warehouse. Subsequent diagnoses of colorectal, lung, and prostate cancer and use of TZD, other antidiabetic agents, and insulin were identified. Cox regression with time-dependent covariates was used to estimate the association between TZD use and cancer risk. Relative risks were adjusted for confounders (age, race/ethnicity, body mass index, use of insulin, and other oral antidiabetic agents).


RESULTS
Of 87,678 individuals, 1,137 had colorectal cancer, 3,246 had prostate cancer, and 1,371 had lung cancer. We observed a 33% reduction in lung cancer risk among TZD users compared with nonusers after adjusting for confounder interactions (relative risk, 0.67; 95% CI, 0.51 to 0.87). The risk reduction for colorectal and prostate cancers did not reach statistical significance.


CONCLUSIONS
TZD use was associated with reduced risk of lung cancer. Further studies are warranted to confirm our findings.
Govindarajan
Rangaswamy
R
Central Arkansas Veterans Health Care System, and the University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA. govindarajanrang@uams.edu
Ratnasinghe
Luke
L
Simmons
Debra L
DL
Siegel
Eric R
ER
Midathada
Madhu V
MV
Kim
Lawrence
L
Kim
Peter J
PJ
Owens
Randall J
RJ
Lang
Nicholas P
NP
D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000368:Aged; D015984:Causality; D003110:Colonic Neoplasms / Q000453:epidemiology*; D015897:Comorbidity; D016001:Confidence Intervals; D003924:Diabetes Mellitus, Type 2 / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D015994:Incidence; D008175:Lung Neoplasms / Q000453:epidemiology*; D008297:Male; D008875:Middle Aged; D011336:Probability; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000453:epidemiology*; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D016019:Survival Analysis; D045162:Thiazolidinediones / Q000627:therapeutic use*
D045162:Thiazolidinediones