Consumption of soft drinks and juices and risk of liver and biliary tract cancers in a European cohort
The aim of the study was to assess associations between intake of combined soft drinks (sugar sweetened and artificially sweetened) and fruit and vegetable juices and the risk of hepatocellular carcinoma (HCC), intrahepatic bile duct (IHBC) and biliary tract cancers (GBTC) using data from the European Prospective Investigation into Cancer and Nutrition cohort of 477,206 participants from 10 European countries.
After 11.4 years of follow-up, 191 HCC, 66 IHBC and 236 GBTC cases were identified. Hazard ratios and 95 % confidence intervals (HR; 95 % CI) were estimated with Cox regression models with multivariable adjustment (baseline total energy intake, alcohol consumption and intake pattern, body mass index, physical activity, level of educational attainment and self-reported diabetes status).
No risk associations were observed for IHBC or GBTC. Combined soft drinks consumption of >6 servings/week was positively associated with HCC risk: HR 1.83; 95 % CI 1.11–3.02, p trend = 0.01 versus non-consumers. In sub-group analyses available for 91 % of the cohort artificially sweetened soft drinks increased HCC risk by 6 % per 1 serving increment (HR 1.06, 95 % CI 1.03–1.09, n cases = 101); for sugar-sweetened soft drinks, this association was null (HR 1.00, 95 % CI 0.95–1.06; n cases = 127, p heterogeneity = 0.07). Juice consumption was not associated with HCC risk, except at very low intakes (<1 serving/week: HR 0.60; 95 % CI 0.38–0.95; p trend = 0.02 vs. non-consumers).
Daily intake of combined soft drinks is positively associated with HCC, but a differential association between sugar and artificially sweetened cannot be discounted. This study provides some insight into possible associations of HCC with sugary drinks intake. Further exploration in other settings is required.
KeywordsHepatocellular carcinoma Biliary tract cancers Soft drink Fruit and vegetable juice Prospective cohort
Intrahepatic bile duct
Type 2 diabetes
Non-alcoholic fatty liver disease
Biliary tract cancer
Extrahepatic bile duct cancer
Ampulla of Vater
European Prospective Investigation into Cancer and Nutrition
Liver-specific alkaline phosphatase
Body mass index
The authors’ responsibilities were as follows—ER: is the overall PI of the EPIC study which is jointly coordinated from ICL and IARC; MS, VF and MJ: conceptualised, designed, obtained funding for and carried out the present research; MS: performed the statistical analysis; and MS, VF, and MJ: contributed to the writing of the manuscript and data interpretation. Contributing authors from each collaborating centres provided the original data and biological samples, information on the respective populations, advice on study design/analysis, and interpretation of the results and approval of the final version of the manuscript for publication. This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA) (Grant Number 2009-139). The coordination of EPIC is financially supported by the European Commission (DG-SANCO); and the International Agency for Research on Cancer. The national cohorts are supported by Danish Cancer Society (Denmark); Ligue Contre le Cancer; Institut Gustave Roussy; Mutuelle Générale de l’Education Nationale; and Institut National de la Santé et de la Recherche Médicale (INSERM) (France); Deutsche Krebshilfe, Deutsches Krebsforschungszentrum (DKFZ); and Federal Ministry of Education and Research (Germany); Stavros Niarchos Foundation; Hellenic Health Foundation; and Ministry of Health and Social Solidarity (Greece); Italian Association for Research on Cancer (AIRC); National Research Council; and AIRE-ONLUS Ragusa, AVIS Ragusa, Sicilian Government (Italy); Dutch Ministry of Public Health, Welfare and Sports (VWS); Netherlands Cancer Registry (NKR); LK Research Funds; Dutch Prevention Funds; Dutch ZON (Zorg Onderzoek Nederland); World Cancer Research Fund (WCRF); and Statistics Netherlands (the Netherlands); European Research Council (ERC) (Grant Number ERC-2009-AdG 232997) and Nordforsk; and Nordic Center of Excellence Programme on Food, Nutrition and Health (Norway); Health Research Fund (FIS); Regional Governments of Andalucía, Asturias, Basque Country, Murcia (No. 6236) and Navarra; and ISCIII RETIC (RD06/0020) and the Catalan Institute of Oncology. (Spain); Swedish Cancer Society; Swedish Scientific Council; and Regional Government of Skåne and Västerbotten (Sweden); Cancer Research UK; Medical Research Council; Stroke Association; British Heart Foundation; Department of Health; Food Standards Agency; and Wellcome Trust (UK). Reagents for the hepatitis infection determinations were kindly provided by Abbott Diagnostics Division, Lyon, France. The funding sources had no influence on the design of the study; the collection, analysis, and interpretation of data; the writing of the report; or the decision to submit the paper for publication.
Conflict of interest
None of the authors had a conflict of interest.
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