Diabetes, abdominal obesity, weight change, metabolic factors and risk of liver cancer in the European Prospective Investigation into Cancer and Nutrition
Final Report Abstract
General obesity has been positively associated with risk of liver cancer and probably with biliary tract cancer, but little is known about abdominal obesity or weight gain during adulthood. We used multivariable Cox proportional hazard models to investigate the associations between weight, body mass index, waist and hip circumference, waist-to-hip and waist-to-height ratio (WHtR), weight change during adulthood and risk of hepatocellular carcinoma (HCC), intra- (IBDC) and extrahepatic bile duct system cancer (EBDSC including gallbladder cancer (GBC)) among 359,525 men and women in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. During a mean follow-up of 8.6 years, 177 cases of HCC, 58 cases of IBDC and 210 cases of EBDSC, including 76 cases of GBC were occurred. All anthropometric measures were positively associated with risk of HCC and GBC. WHtR showed the strongest association with HCC (relative risk (RR) comparing extreme tertiles 3.51, 95% confidence interval (95% CI): 2.09-5.87; Ptrend<0.0001) and with GBC (RR: 1.52, 95% CI: 1.09-2.11 for an increment of one unit in WHtR). Weight gain during adulthood was also positively associated with HCC when comparing extreme tertiles (RR: 2.48, 95% CI: 1.49-4.13; Ptrend = 0.0003). No statistically significantly association was observed between obesity and risk of IBDC and EBDSC. Our results provide evidence of an association between obesity, particularly abdominal obesity, and risk of HCC and GBC in Europe. Furthermore, the evidence on associations between type 2 diabetes, diabetes duration, age at diabetes diagnosis, insulin treatment, and risk of biliary tract cancer (BTC) and hepatocellular carcinoma (HCC), independent of general and abdominal obesity is scarce. Thus, we conducted a prospective analysis in the EPIC-cohort study among 363 426 participants with self-reported diabetes data. Multivariable adjusted relative risks and 95% confidence intervals were estimated from Cox regression models. In a nested case-control subset, analyses were carried out in HCV/HBV-negative individuals. During 8.5 years of follow-up, 204 BTC cases [including 75 gallbladder cancer (GBC) cases], and 176 HCC cases were identified. Independent of body mass index and waist-to-height ratio diabetes status was associated with higher risk of BTC and HCC [1.77 (1.00–3.13) and 2.17 (1.36–3.47)]. For BTC, the risk seemed to be higher in participants with shorter diabetes duration and those not treated with insulin. Regarding cancer subsites, diabetes was only associated with GBC [2.72 (1.17–6.31)]. The risk for HCC was particularly higher in participants treated with insulin. The results were not appreciably different in HCV/HBV-negative individuals. This findings supports the hypothesis that diabetes is a risk factor for BTC ( particularly GBC) and HCC.Overall, the highest risk for HCC and GBC was observed for individuals with both, obesity and type 2 diabetes.
Publications
- Abdominal Obesity, Weight Gain during Adulthood and Risk of Liver and Biliary Tract Cancer in a European Cohort; Int J Cancer. 2013 Feb 1;132(3):645-57
Schlesinger S, Aleksandrova K, Pischon T, Fedirko V, Jenab M, Trepo E, Boffetta P, Dahm CC, Overvad K, Tjønneland A, Halkjær J, Fagherazzi G, Boutron-Ruault MC, Carbonnel F, Kaaks R, Lukanova A, Boeing H, Trichopoulou A, Bamia C, Lagiou P, Palli D, Grioni S, Panico S, Tumino R, Vineis P, Bueno-de-Mesquita HB, van den Berg S, Peeters PHM, Braaten T, Weiderpass, Quirós JR, Travier N, Sánchez MJ, Navarro, Barricarte CA, Dorronsoro M, Lindkvist B, Regner S, Werner M, Sund M, Khaw KT, Wareham N, Travis RC, Norat T, Wark PA, Riboli E, Nöthlings U
(See online at https://doi.org/10.1002/ijc.27645) - Diabetes mellitus, insulin treatment, diabetes duration, and risk of biliary tract cancer and hepatocellular carcinoma in a European cohort. Ann Oncol. 2013 Sep;24(9):2449-55
Schlesinger S, Aleksandrova K, Pischon T, Jenab M, Fedirko V, Trepo E, Overvad K, Roswall N, Tjønneland A, Boutron-Ruault MC, Fagherazzi G, Racine A, Kaaks R, Grote VA, Boeing H, Trichopoulou A, Pantzalis M, Kritikou M, Mattiello A, Sieri S, Sacerdote C, Palli D, Tumino R, Peeters PH, Bueno-de-Mesquita HB, Weiderpass E, Quirós JR, Zamora-Ros R, Sánchez MJ, Arriola L, Ardanaz E, Tormo MJ, Nilsson P, Lindkvist B, Sund M, Rolandsson O, Khaw KT, Wareham N, Travis RC, Riboli E, Nöthlings U
(See online at https://doi.org/10.1093/annonc/mdt204) - Inflammatory and metabolic biomarkers and risk of liver and bilary tract cancer. Hepatology Vol 60 Issue 3, September 2014, Pages 858-871
Aleksandrova K, Boeing H, Nöthlings U, Jenab M, Fedirko V, Kaaks R, Lukanova A, Trichopoulou A, Trichopoulos D, Boffetta P, Trepo E, Westhpal S, Duarte-Salles T, Stepien M, Overvad K, Tjonneland A, Halkjaer J, Boutron-Ruault MC, Dossus L, Racine A, Lagiou
(See online at https://doi.org/10.1002/hep.27016)
