Type 2 diabetes mellitus (DM2) has been associated with hepatocellular carcinoma (HCC) development. To study this relationship, we enrolled 465 HCC patients compared with 618 Cirrhotic cases and 490 Controls. The prevalence of DM2 is significantly higher in HCC patients with an Odds Ratio of 3.12 versus Controls. In HCC cases with alcohol abuse, the frequency of DM2 is the highest. In our HCC patients, when HCV infection is associated with alcohol abuse, the liver cancer develops earlier. In addition, multivariate analysis shows that alcohol consumption is an independent risk factor for HCC more relevant than HCV infection.
References
[1]
World Health Organization. Mortality database. Available online: http://www.who.int/whosis/whostat/EN_WHS08_Part1.pdf (accessed on 4 December 2008).
[2]
Armstrong, GL; Alter, MJ; McQuillan, GM; Margolis, HS. The past incidence of hepatitis C virus infection: implications for the future burden of chronic liver disease in the United States. Hepatology?2003, 1, 777–782.
[3]
Davila, JA; Morgan, RO; Shaib, Y; McGlynn, KA; El-Serag, HB. Diabetes increases the risk of hepatocellular carcinoma in the United States: a population based case control study. Gut?2005, 54, 533–539.
[4]
Metascreen Writing Committee; Bonadonna, RC; Cucinotta, D; Fedele, D; Riccardi, G; Tiengo, A. The metabolic syndrome is a risk indicator of microvascular and macrovascular complications in diabetes: results from Metascreen, a multicenter diabetes clinic-based survey. Diabetes Care?2006, 29, 2701–2707.
[5]
Sloan, FA; Bethel, A; Ruiz, D; Shea, AH; Feinglos, MN. The growing burden of diabetes mellitus in the US elderly population. Arch. Intern. Med?2008, 168, 192–199.
[6]
Bugianesi, E; Leone, N; Vanni, E; Marchesini, G; Brunello, F; Carucci, P; Musso, A; De Polis, P; Capussotti, L; Salizzoni, M; Rizzetto, M. Expanding the natural history of nonalcoholic steatohepatitis: from cryptogenic cirrhosis to hepatocellular carcinoma. Gastroenterology?2002, 123, 134–140.
[7]
Moscatiello, S; Manini, R; Marchesini, G. Diabetes and liver disease: an ominous association. Nutr. Metab. Cardiovasc. Dis?2007, 17, 63–70.
[8]
El-Serag, HB; Richardson, PA; Everhart, JE. The role of diabetes in hepatocellular carcinoma: a case-control study among United States veterans. Am. J. Gastroenterol?2001, 96, 2462–2467.
[9]
Verlato, G; Bonora, E; Zoppini, G; Muggeo, M. Mortality from site-specific malignancies in type 2 diabetic patients from Verona. Diabetes Care?2003, 26, 1047–1051.
[10]
Coughlin, SS; Calle, EE; Teras, LR; Petrelli, J; Thun, MJ. Diabetes mellitus as a predictor of cancer mortality in a large cohort of US adults. Am. J. Epidemiol?2004, 159, 1160–1167.
[11]
El Serag, HB; Tran, T; Everhart, JE. Diabetes increases the risk of chronic liver disease and hepatocellular carcinoma. Gastroenterology?2004, 126, 460–468.
[12]
Chen, CL; Yang, HI; Yang, WS; Liu, CJ; Chen, PJ; You, SL; Wang, LY; Sun, CA; Lu, SN; Chen, DS; Chen, CJ. Metabolic factors and risk of hepatocellular carcinoma by chronic hepatitis B/C infection: a follow-up study in Taiwan. Gastroenterology?2008, 135, 111–121.
[13]
Inoue, M; Iwasaki, M; Otani, T; Sasazuki, S; Noda, M; Tsugane, S. Diabetes mellitus and the risk of cancer: results from a large-scale population-based cohort study in Japan. Arch. Intern. Med?2006, 166, 1871–1877.
[14]
Lai, MS; Hsieh, MS; Chiu, YH; Chen, THH. Type 2 diabetes and hepatocellular carcinoma: a cohort study in high prevalence area of hepatitis virus infection. Hepatology?2006, 43, 1295–1302.
[15]
Donadon, V; Balbi, M; Casarin, P; Alberti, A. Association between hepatocellular carcinoma and type 2 diabetes mellitus in Italy: Potential role of insulin. World J. Gastroenterol?2008, 14, 5695–700.
[16]
Hassan, MM; Hwang, LY; Hatten, CJ; Swaim, M; Donghui, L; Abbruzzese, JL; Beasley, P; Patt, YZ. Risk factors for hepatocellular carcinoma. Synergism of alcohol with viral hepatitis and diabetes mellitus. Hepatology?2002, 36, 1206–1213.
[17]
Yuan, JM; Govindarajan, S; Arakawa, K; Yu, M. Synergism of alcohol, diabetes and viral hepatitis on the risk of hepatocellular carcinoma in blacks and whites in the US. Cancer?2004, 101, 1009–1017.
[18]
Llovet, JM; Beaugrand, M. Hepatocellular carcinoma: present status and future prospects. J. Hepato?2003, 38, S136–S149.
[19]
De Paschale, M; Biagiotti, S; Chianese, R. Variazione nel tempo della prevalenza dei marcatori dell’epatite B in donatori di sangue. La trasfusione del sangue?2001, 46, 335–340.
[20]
Pilotto, L; Gaggioli, A; Lo Noce, C; Dima, F; Palmieri, L; Uguccioni, M; Pede, S; Giampaoli, S; Vanuzzo, D. Diabetes in Italy: a public health problem. Ital. Heart. J. Suppl?2004, 5, 480–486.
[21]
Bellentani, S; Miglioli, L; Bedogni, G; Crocè, LS; Tiribelli, C. Epidemiology of hepatitis C virus infection. Minerva. Gastroenterol. Dietol?2005, 51, 15–29.
[22]
Bellentani, S; Tiribelli, C; Saccoccio, G; Sodde, M; Fratti, M; De Martin, C; Cristianini, G. Prevalence of chronic liver disease in the general population of Northern Italy: The dionysos study. Hepatology?1994, 20, 1442–1449.
[23]
National Diabetes Data Group. Classification and diagnosis of diabetes mellitus and other categories of glucose intolerance. Diabetes?1979, 28, 1039–1057.
[24]
American Diabetes Association. Report of the expert committee on the diagnosis and classification of diabetes mellitus. Diabetes Care?2003, 26, S5–S20.
[25]
Corrao, G; Lepore, AR; Torchio, P; Valenti, M; Galatola, G; D’amicis, A; Arico, S; di Orio, F. The effect of drinking coffee and smoking cigarettes on the risk of cirrhosis associated with alcohol consumption. A case-control study. Provincial group for the study of chronic liver disease. Eur. J. Epidemiol?1994, 10, 657–664.
[26]
Rothman, KJ. The estimation of synergy or antagonism. Am. J. Epidemiol?1976, 103, 506–511.
[27]
McKeown-Eyssen, G. Epidemiology of colorectal cancer revisited: are serum triglycerides and/or plasma glucose associated with risk? Cancer Epidemiol. Biomarkers. Prev?1994, 3, 687–695.
[28]
Giovannucci, E. Insulin and colon cancer. Cancer Causes Control?1995, 6, 164–179.
[29]
Giovannucci, E. Nutrition, insulin, insulin-like growth factors and cancer. Horm. Metab. Res?2003, 35, 694–704.
[30]
Balkau, B; Kahn, HS; Courbon, D; Eschwege, E; Ducimetiere, P. Hyperinsulinemia predicts fatal liver cancer but is inversely associated with fatal cancer at some other sites. Diabetes Care?2001, 24, 843–849.
[31]
Carlsson, S; Hammar, N; Grill, V. Alcohol consumption and type 2 diabetes. Diabetologia?2005, 48, 1051–1054.
[32]
Rosen, P; Nawroth, PP; King, G; Moller, W; Tritschler, HJ; Packer, L. The role of oxidative stress in the onset and progression of diabetes and its complications: a summary of a congress Series sponsored by UNESCO-MCBN, the American Diabetes Association and the German Diabetes Society. Diabetes Metab. Res. Rev?2001, 17, 189–212.
[33]
Kar, M; Chakraborti, AS. Release of iron from haemoglobin a possible source of free radicals in diabetes mellitus. Indian J. Exp. Boil?1999, 37, 190–192.
[34]
Ford, ES; Cogswell, ME. Diabetes and serum ferritin concentration among US adults. Diabetes Care?1999, 22, 1978–1983.
Petersen, DR. Alcohol, iron-associated oxidative stress and cancer. Alcohol?2005, 35, 243–249.
[42]
Wang, XD. Alcohol, vitamin A and cancer. Alcohol?2005, 35, 251–258.
[43]
De Marco, R; Locatelli, F; Zoppini, G; Verlato, G; Bonora, E; Muggeo, M. Cause-specific mortality in type 2 diabetes: The Verona diabetes study. Diabetes Care?1999, 22, 756–761.
[44]
Tolman, KG; Fonseca, V; Dalpiaz, A; Tan, MH. Spectrum of liver disease in type 2 diabetes and management of patients with diabetes and liver disease. Diabetes Care?2007, 30, 734–743.