Antidiabetic Therapies Affect Risk of Pancreatic Cancer

被引:542
作者
Li, Donghui [1 ]
Yeung, Sai-Ching J. [2 ]
Hassan, Manal M.
Konopleva, Marina [3 ]
Abbruzzese, James L.
机构
[1] Univ Texas MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Unit 426, Houston, TX 77030 USA
[2] Univ Texas MD Anderson Canc Ctr, Dept Endocrine Neoplasia & Hormonal Disorders, Houston, TX 77030 USA
[3] Univ Texas MD Anderson Canc Ctr, Dept Leukemia, Houston, TX 77030 USA
基金
美国国家卫生研究院;
关键词
DIABETES-MELLITUS; METFORMIN; KINASE; ASSOCIATION; PREVALENCE; PREVENTION; MORTALITY; DRUGS; AMPK;
D O I
10.1053/j.gastro.2009.04.013
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
BACKGROUND & AIMS: Antidiabetic drugs have been found to have various effects on cancer in experimental systems and in epidemiologic studies, although the association between these therapeutics and the risk of human pancreatic cancer has not been explored. We investigated the effect of antidiabetic therapies on the risk of pancreatic cancer. METHODS: A hospital-based case-control study was conducted at M. D. Anderson Cancer Center from 2004 to 2008 involving 973 patients with pancreatic adenocarcinoma (including 259 diabetic patients) and 863 controls (including 109 diabetic patients). Information on diabetes history and other risk factors was collected by personal interview. The frequencies of use of insulin, insulin secretagogues, metformin, and other antidiabetic medications among diabetic patients were compared between cases and controls. The risk of pancreatic cancer was estimated using unconditional logistic regression analysis. RESULTS: Diabetic patients who had taken metformin had a significantly lower risk of pancreatic cancer compared with those who had not taken metformin (odds ratio, 0.38; 95% confidence interval, 0.22-0.69; P = .001), with adjustments for potential confounders. This difference remained statistically significant when the analysis was restricted to patients with a duration of diabetes >2 years or those who never used insulin. In contrast, diabetic patients who had taken insulin or insulin secretagogues had a significantly higher risk of pancreatic cancer compared with diabetic patients who had not taken these drugs. CONCLUSIONS: Metformin use was associated with reduced risk, and insulin or insulin secretagogue use was associated with increased risk of pancreatic cancer in diabetic patients.
引用
收藏
页码:482 / 488
页数:7
相关论文
共 32 条
[11]   Accuracy of patients' reports of comorbid disease and their association with mortality in ESRD [J].
Cavanaugh, Kerri L. ;
Merkin, Sharon Stein ;
Plantinga, Laura C. ;
Fink, Nancy E. ;
Sadler, John H. ;
Powe, Neil R. .
AMERICAN JOURNAL OF KIDNEY DISEASES, 2008, 52 (01) :118-127
[12]   Pancreatic cancer-associated diabetes mellitus: Prevalence and temporal association with diagnosis of cancer [J].
Chari, Suresh T. ;
Leibson, Cynthia L. ;
Rabe, Kari G. ;
Timmons, Lawrence J. ;
Ransom, Jeanine ;
De Andrade, Mariza ;
Petersen, Gloria M. .
GASTROENTEROLOGY, 2008, 134 (01) :95-101
[13]  
DILMAN VM, 1978, ARCH GESCHWULSTFORSC, V48, P1
[14]   Physiological concentrations of insulin augment pancreatic cancer cell proliferation and glucose utilization by activating MAP kinase, PI3 kinase and enhancing GLUT-1 expression [J].
Ding, XZ ;
Fehsenfeld, DM ;
Murphy, LO ;
Permert, J ;
Adrian, TE .
PANCREAS, 2000, 21 (03) :310-320
[15]   Metformin and reduced risk of cancer in diabetic patients [J].
Evans, JMM ;
Donnelly, LA ;
Emslie-Smith, AM ;
Alessi, DR ;
Morris, AD .
BMJ-BRITISH MEDICAL JOURNAL, 2005, 330 (7503) :1304-1305
[16]   DIABETES-MELLITUS AS A RISK FACTOR FOR PANCREATIC-CANCER - A METAANALYSIS [J].
EVERHART, J ;
WRIGHT, D .
JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1995, 273 (20) :1605-1609
[17]   The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways [J].
Fryer, LGD ;
Parbu-Patel, A ;
Carling, D .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (28) :25226-25232
[18]   The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas [J].
Govannucci, Edward ;
Michaud, Dominique .
GASTROENTEROLOGY, 2007, 132 (06) :2208-2225
[19]   Targeting AMPK: A new therapeutic opportunity in breast cancer [J].
Hadad, Sirwan M. ;
Fleming, Stewart ;
Thompson, Alastair M. .
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2008, 67 (01) :1-7
[20]   Risk factors for pancreatic cancer: Case-control study [J].
Hassan, Manal M. ;
Bondy, Melissa L. ;
Wolff, Robert A. ;
Abbruzzese, James L. ;
Vauthey, Jean-Nicolas ;
Pisters, Peter W. ;
Evans, Douglas B. ;
Khan, Rabia ;
Chou, Ta-Hsu ;
Lenzi, Renato ;
Jiao, Li ;
Li, Donghui .
AMERICAN JOURNAL OF GASTROENTEROLOGY, 2007, 102 (12) :2696-2707