title: Diabetes and Insulin Therapy, but Not Metformin, Are Related to Hepatocellular Cancer Risk.
abstract: Introduction. Metabolic conditions, including type 2 diabetes, have been related to hepatocellular carcinoma (HCC) risk. We have further analyzed the role of diabetes and antidiabetic treatments on HCC. Methods. Data derived from a hospital-based case-control study (Italy, 2005-2012) on 224 HCC patients and 389 controls. Odds ratios (ORs) were estimated using multiple logistic regression models. Results. Sixty-nine (30.9%) cases versus 52 (13.5%) controls reported a diabetes diagnosis, corresponding to a multivariate OR of 2.25 (95% confidence interval, CI = 1.42-3.56). A stronger excess risk emerged for a longer time since diabetes diagnosis (OR = 2.96 for <10 years and 5.33 for ≥10 years). Oral therapies were inversely, though not significantly, related to HCC risk, OR being 0.44 for metformin and 0.88 for sulfonylureas; conversely, insulin was nonsignificantly directly associated (OR = 1.90). Compared to nondiabetic subjects who were never smokers, those who were diabetics and ever smokers had an OR of 6.61 (95% CI 3.31-13.25). Conclusion. Our study confirms an over 2-fold excess HCC risk in diabetics, with a stronger excess risk in diabetic subjects who are also tobacco smokers. Metformin may decrease the risk of HCC, whereas insulin may increase the risk.
authors.affiliation: Institute of Internal Medicine, Catholic University of Rome, Largo Francesco Vito 1, 00168 Rome, Italy ; Internal Medicine and Gastroenterology Unit, Complesso Integrato Columbus, Via Giuseppe Moscati 31-33, 00168 Rome, Italy.
authors.forename: Luca
authors.identifier: 0000-0003-3464-0068
authors.initials: L
authors.lastname: Miele
authors.affiliation: Department of Epidemiology, IRCCS-"Mario Negri" Institute for Pharmacological Research, Via G. La Masa 19, 20156 Milan, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Bosetti
authors.affiliation: Department of Epidemiology, IRCCS-"Mario Negri" Institute for Pharmacological Research, Via G. La Masa 19, 20156 Milan, Italy.
authors.forename: Federica
authors.identifier: 0000-0002-5841-5773
authors.initials: F
authors.lastname: Turati
authors.affiliation: Institute of Internal Medicine, Catholic University of Rome, Largo Francesco Vito 1, 00168 Rome, Italy ; Internal Medicine and Gastroenterology Unit, Complesso Integrato Columbus, Via Giuseppe Moscati 31-33, 00168 Rome, Italy.
authors.forename: Gianlodovico
authors.initials: G
authors.lastname: Rapaccini
authors.affiliation: Institute of Internal Medicine, Catholic University of Rome, Largo Francesco Vito 1, 00168 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Gasbarrini
authors.affiliation: Department of Clinical Sciences and Community Health, University of Milan, Via G. Venezian 1, 20122 Milan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: La Vecchia
authors.affiliation: Institute of Public Health Section of Hygiene, Catholic University of Rome, Largo Francesco Vito 1, 00168 Rome, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Boccia
authors.affiliation: Institute of Internal Medicine, Catholic University of Rome, Largo Francesco Vito 1, 00168 Rome, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Grieco