Metformin and Cancer Risk in Diabetic Patients: A Systematic Review and Meta-analysis

被引：698

作者：

DeCensi, Andrea ^{[1
,2
]}

Puntoni, Matteo ^{[1
]}

Goodwin, Pamela ^{[4
,5
]}

Cazzaniga, Massimiliano ^{[2
]}

Gennari, Alessandra ^{[1
]}

Bonanni, Bernardo ^{[2
]}

Gandini, Sara ^{[3
]}

机构：

[1] EO Osped Galliera, Med Oncol Unit, I-16128 Genoa, Italy

[2] European Inst Oncol, Div Canc Prevent & Genet, Milan, Italy

[3] European Inst Oncol, Div Epidemiol & Biostat, Milan, Italy

[4] Univ Toronto, Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada

[5] Univ Toronto, Princess Margaret Hosp, Toronto, ON M5G 1X5, Canada

来源：

CANCER PREVENTION RESEARCH | 2010年 / 3卷 / 11期

关键词：

ACTIVATED PROTEIN-KINASE; BREAST-CANCER; METABOLIC SYNDROME; PANCREATIC-CANCER; CELL-GROWTH; HEPATOCELLULAR-CARCINOMA; POSTMENOPAUSAL WOMEN; INSULIN-RESISTANCE; FOLLOW-UP; C-PEPTIDE;

D O I：

10.1158/1940-6207.CAPR-10-0157

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Metformin, an insulin-lowering agent, has been associated with decreased cancer risk in epidemiologic studies in diabetic patients. We performed a comprehensive literature search and meta-analysis of epidemiologic studies to assess the effect of metformin on cancer incidence and mortality in diabetic patients, using Pubmed, ISI Web of Science, Embase, and the Cochrane library until May 2009, with no language or time restrictions. Independent reports with sufficient information to allow risk estimation of cancer risk/mortality and a measure of uncertainty were reviewed and cross-checked independently by three investigators. Eleven studies were selected for relevance in terms of intervention, population studied, independence, and reporting of cancer incidence or mortality data, reporting 4,042 cancer events and 529 cancer deaths. A 31% reduction in overall summary relative risk (0.69; 95% confidence interval, 0.61-0.79) was found in subjects taking metformin compared with other antidiabetic drugs. The inverse association was significant for pancreatic and hepatocellular cancer, and nonsignificant for colon, breast, and prostate cancer. A trend to a dose-response relationship was noted. Metformin is associated with a decreased risk of cancer incidence compared with other treatments among diabetic patients. Given the retrospective nature of most studies and the possibility that the control treatments increase risk, phase II trials are needed before large cancer prevention trials are launched. Cancer Prev Res; 3(11); 1451-61. (C) 2010 AACR.

引用

页码：1451 / 1461

页数：11

共 73 条

[1] Metabolic syndrome and postmenopausal breast cancer in the ORDET cohort: A nested case-control study [J].

Agnoli, C. ;

Berrino, F. ;

Abagnato, C. A. ;

Muti, P. ;

Panico, S. ;

Crosignani, P. ;

Krogh, V. .

NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES, 2010, 20 (01) :41-48

[2] LKB1-dependent signaling pathways [J].

Alessi, Dario R. ;

Sakamoto, Kei ;

Bayascas, Jose R. .

ANNUAL REVIEW OF BIOCHEMISTRY, 2006, 75 :137-163

[3] Metformin blocks the stimulative effect of a high-energy diet on colon carcinoma growth in vivo and is associated with reduced expression of fatty acid synthase [J].

Algire, Carolyn ;

Amrein, Lilian ;

Zakikhani, Mahvash ;

Panasci, Lawrence ;

Pollak, Michael .

[4] Metformin inhibits breast cancer cell growth, colony formation and induces cell cycle arrest in vitro [J].

Alimova, Irina N. ;

Liu, Bolin ;

Fan, Zeying ;

Edgerton, Susan M. ;

Dillon, Thomas ;

Lind, Stuart E. ;

Thor, Ann D. .

CELL CYCLE, 2009, 8 (06) :909-915

[5] Insulin Receptor Isoforms and Insulin Receptor/Insulin-Like Growth Factor Receptor Hybrids in Physiology and Disease [J].

Belfiore, Antonino ;

Frasca, Francesco ;

Pandini, Giusepe ;

Sciacca, Laura ;

Vigneri, Riccardo .

ENDOCRINE REVIEWS, 2009, 30 (06) :586-623

[6] The antidiabetic drug metformin exerts an antitumoral effect in vitro and in vivo through a decrease of cyclin D1 level [J].

Ben Sahra, I. ;

Laurent, K. ;

Loubat, A. ;

Giorgetti-Peraldi, S. ;

Colosetti, P. ;

Auberger, P. ;

Tanti, J. F. ;

Le Marchand-Brustel, Y. ;

Bost, F. .

ONCOGENE, 2008, 27 (25) :3576-3586

[7] Long-Term Metformin Use Is Associated With Decreased Risk of Breast Cancer [J].

Bodmer, Michael ;

Meier, Christian ;

Krahenbuehl, Stephan ;

Jick, Susan S. ;

Meier, Christoph R. .

DIABETES CARE, 2010, 33 (06) :1304-1308

[8] Increased cancer-related mortality for patients with type 2 diabetes who use sulforrylureas or insulin [J].

Bowker, SL ;

Majumdar, SR ;

Veugelers, P ;

Johnson, JA .

DIABETES CARE, 2006, 29 (02) :254-258

[9] 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study [J].

Bray, G. A. ;

Chatellier, A. ;

Duncan, C. ;

Greenway, F. L. ;

Levy, E. ;

Ryan, D. H. ;

Polonsky, K. S. ;

Tobian, J. ;

Ehrmann, D. ;

Matulik, M. J. ;

Clark, B. ;

Czech, K. ;

DeSandre, C. ;

Hilbrich, R. ;

McNabb, W. ;

Semenske, A. R. ;

Goldstein, B. J. ;

Smith, K. A. ;

Wildman, W. ;

Pepe, C. ;

Goldberg, R. B. ;

Calles, J. ;

Ojito, J. ;

Castillo-Florez, S. ;

Florez, H. J. ;

Giannella, A. ;

Lara, O. ;

Veciana, B. ;

Haffner, S. M. ;

Montez, M. G. ;

Lorenzo, C. ;

Martinez, A. ;

Hamman, R. F. ;

Testaverde, L. ;

Bouffard, A. ;

Dabelea, D. ;

Jenkins, T. ;

Lenz, D. ;

Perreault, L. ;

Price, D. W. ;

Steinke, S. C. ;

Horton, E. S. ;

Poirier, C. S. ;

Swift, K. ;

Caballero, E. ;

Jackson, S. D. ;

Lambert, L. ;

Lawton, K. E. ;

Ledbury, S. ;

Kahn, S. E. .

LANCET, 2009, 374 (9702) :1677-1686

[10] Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth [J].

Buzzai, Monica ;

Jones, Russell G. ;

Amaravadi, Ravi K. ;

Lum, Julian J. ;

DeBerardinis, Ralph J. ;

Zhao, Fangping ;

Viollet, Benoit ;

Thompson, Craig B. .

CANCER RESEARCH, 2007, 67 (14) :6745-6752

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