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Cause of death statistics. 2012; Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.mohwgovtw\/cht\/DOS\/Statisticaspx?f_list_no=312&fod_list_no=2747\" xlink:type=\"simple\">www.mohwgovtw\/cht\/DOS\/Statisticaspx?f_list_no=312&amp;fod_list_no=2747<\/ext-link> Accessed 4 June 2013."},{"key":"ref3","doi-asserted-by":"crossref","first-page":"1674","DOI":"10.2337\/dc10-0666","article-title":"Diabetes and cancer: a consensus report","volume":"33","author":"E Giovannucci","year":"2010","journal-title":"Diabetes Care"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"242","DOI":"10.1016\/j.metabol.2011.06.020","article-title":"The association of diabetes mellitus with liver, colon, lung, and prostate cancer is independent of hypertension, hyperlipidemia, and gout in Taiwanese patients","volume":"61","author":"MY Lee","year":"2012","journal-title":"Metabolism"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1038\/nrc2536","article-title":"Insulin and insulin-like growth factor signalling in neoplasia","volume":"8","author":"M Pollak","year":"2008","journal-title":"Nat Rev Cancer"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1158\/0008-5472.CAN-06-1712","article-title":"Down-regulation of type I insulin-like growth factor receptor increases sensitivity of breast cancer cells to insulin","volume":"67","author":"H Zhang","year":"2007","journal-title":"Cancer Res"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1478-811X-7-14","article-title":"Expression and function of the insulin receptor substrate proteins in cancer","volume":"7","author":"K Mardilovich","year":"2009","journal-title":"Cell Commun Signal"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"3109S","DOI":"10.1093\/jn\/131.11.3109S","article-title":"Insulin, insulin-like growth factors and colon cancer: a review of the evidence","volume":"131","author":"E Giovannucci","year":"2001","journal-title":"J Nutr"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1126\/science.1160809","article-title":"Understanding the Warburg effect: the metabolic requirements of cell proliferation","volume":"324","author":"MG Vander Heiden","year":"2009","journal-title":"Science"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"2569","DOI":"10.1158\/1055-9965.EPI-09-0372","article-title":"Obesity and cancer: the role of dysfunctional adipose tissue","volume":"18","author":"RC van Kruijsdijk","year":"2009","journal-title":"Cancer Epidemiol Biomarkers Prev"},{"key":"ref11","first-page":"226","article-title":"Influence of insulin deprivation on growth of the 7,12-dimethylbenz(a)anthracene-induced mammary carcinoma in rats subjected to alloxan diabetes and food restriction","volume":"32","author":"JC Heuson","year":"1972","journal-title":"Cancer Res"},{"key":"ref12","unstructured":"Administration NHI, Ministry of Health and Welfare, Taiwan. Statistical annual reports. Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.nhigovtw\/webdata\/webdataaspx?menu=17&menu_id=1023&WD_ID=1043&webdata_id=3351\" xlink:type=\"simple\">www.nhigovtw\/webdata\/webdataaspx?menu=17&amp;menu_id=1023&amp;WD_ID=1043&amp;webdata_id=3351<\/ext-link>."},{"key":"ref13","unstructured":"Welfare MoHa, Taiwan. Cancer registry annual report. 2010; Available: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.hpagovtw\/BHPNet\/Web\/Stat\/StatisticsShowaspx?No=201305060001\" xlink:type=\"simple\">www.hpagovtw\/BHPNet\/Web\/Stat\/StatisticsShowaspx?No=201305060001<\/ext-link> Accessed 6 May 2013."},{"key":"ref14","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1038\/ajg.2011.384","article-title":"Risk of hepatocellular carcinoma in diabetic patients and risk reduction associated with anti-diabetic therapy: a population-based cohort study","volume":"107","author":"SW Lai","year":"2012","journal-title":"Am J Gastroenterol"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"2506","DOI":"10.3748\/wjg.15.2506","article-title":"Antidiabetic therapy and increased risk of hepatocellular carcinoma in chronic liver disease","volume":"15","author":"V Donadon","year":"2009","journal-title":"World J 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glucose-lowering therapies on cancer risk in type 2 diabetes","volume":"52","author":"CJ Currie","year":"2009","journal-title":"Diabetologia"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1007\/s00592-008-0083-2","article-title":"Sulphonylureas and cancer: a case-control study","volume":"46","author":"M Monami","year":"2009","journal-title":"Acta Diabetol"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1007\/s10552-009-9407-y","article-title":"Metformin use and prostate cancer in Caucasian men: results from a population-based case-control study","volume":"20","author":"JL Wright","year":"2009","journal-title":"Cancer Causes Control"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"1451","DOI":"10.1158\/1940-6207.CAPR-10-0157","article-title":"Metformin and cancer risk in diabetic patients: a systematic review and meta-analysis","volume":"3","author":"A Decensi","year":"2010","journal-title":"Cancer Prev Res 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