In contrast, metformin was associated with a decreased risk for liver cancer.

Consistent with previous in vitro studies on TZDs which showed antiproliferation and prodifferentiation effects, our data have provided an association between the clinical use of TZDs and a reduced risk for several cancer incidences, in particular liver cancer. The association became stronger when the duration of TZD use was longer and the dosage was higher. Rosiglitazone, but not pioglitazone, was associated with a significantly reduced risk for colorectal cancer. STA-9090 No association between both TZDs and lung and bladder cancer was observed. Previous reports on the association between TZD use and cancer incidence have been inconsistent. The report from the data obtained from the Veterans Integrated Services Network 16 (VISN 16) cohort of 87,678 individuals showed a 33% reduction in lung cancer risk among TZD users compared with nonusers (relative risk: 0.65, 95% CI: 0.51-0.87). However, as rosiglitazone and pioglitazone were combined, the risk reduction

for colorectal PF-562271 in vitro cancer did not reach statistical significance. 18 In contrast, the present study results did not show a decreased risk for lung cancer. Although numerous in vitro studies support the protective effect of TZDs in lung cancer, the specific tissue or type of cancer and its stage might contribute to the efficacy or failure of TZDs as antineoplastic agents. 19, 20, 24-29 Because the risk factors, genetic expressions, and pharmaceutical responses of lung cancer of the Taiwanese differ significantly from those in the Western countries, there might also be a differential response to TZDs. 30 On the contrary, our analysis showed a protective effect of rosiglitazone on colorectal cancers, which was not evident in the VISN 16 cohort. In animal studies, PPAR-γ agonists inhibited tumor growth

and colon carcinogenesis through induction of apoptosis and suppression of the cell cycle. 31-34 The current study, to the best of our knowledge, provides the first evidence that rosiglitazone but not pioglitazone might reduce Masitinib (AB1010) the risk of colorectal cancer. It is initially surprising that both pioglitazone and rosiglitazone are associated with a reduced risk for liver cancer. Hepatocellular carcinoma, one of the most incident, prevalent, and lethal malignancies in Taiwan, is regarded as a late-stage sequel of chronic infection of hepatitis B and C. 35, 36 With only a few exceptions, the development of hepatocellular carcinoma almost exclusively follows the sequence of chronic hepatic inflammation, cirrhosis of the liver, repair and regeneration of hepatic cells, and then carcinogenesis. 37 This might explain the finding that risk reduction was more evident in the patients with chronic liver disease. Despite the concern that physicians may preferentially prescribe TZDs to patients with better liver function (i.e.