Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes
Thiazolidinediones and the risk of lung, prostate, and colon cancer in patients with diabetes
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DOI：
10.1200/jco.2006.07.2777
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发表时间：
2007-04-20
影响因子：
45.3
通讯作者：
Lang, Nicholas P.
中科院分区：
文献类型：
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作者：
Govindarajan, Rangaswamy;Ratnasinghe, Luke;Lang, Nicholas P.
目的过氧化物酶体增殖物激活受体γ（Peroxisome Proliferator-Activated Receptor gamma，PPAR gamma）介导细胞周期阻滞和脂肪细胞分化;在脂肪肉瘤、肺癌和前列腺癌中具有肿瘤抑制活性;抑制腺瘤性结肠息肉病（Adenomatous Polyposis coli，APC）（min/+）小鼠结肠息肉形成。为了评估噻唑烷二酮（TZD）的影响，TZD是用于治疗糖尿病的PPAR γ配体，对10个退伍军人事务医疗中心的数据库进行了回顾性分析。患者和方法1997年至2003年期间40岁及以上诊断为糖尿病的男性患者的数据来自退伍军人综合服务网络16（VISN16）数据仓库随后诊断为结直肠癌、肺癌和前列腺癌，并使用TZD、其他降糖药和胰岛素。使用时间依赖性协变量的考克斯回归来估计TZD使用与癌症风险之间的关联。调整混杂因素（年龄、种族/民族、体重指数、使用胰岛素和其他口服降糖药）的相对危险度。结果在87，678例受试者中，1，137例患有结直肠癌，3，246例患有前列腺癌，1，371例患有肺癌。在调整混杂因素相互作用后，我们观察到TZD使用者与非使用者相比肺癌风险降低33%（相对风险，0.67; 95%CI，0.51至0.87）。结直肠癌和前列腺癌的风险降低没有达到统计学意义。结论TZD的使用与肺癌的风险降低。需要进一步的研究来证实我们的发现。
Purpose Peroxisome proliferator-activated receptor gamma (PPAR gamma) 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 gamma ligands used to treat diabetes mellitus, a retrospective analysis of a database from 10 Veteran Affairs medical centers was conducted.Patients and 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.Conclusion TZD use was associated with reduced risk of lung cancer. Further studies are warranted to confirm our findings.