%0 Journal Article
%A Fedirko, Veronika
%A Tran, Hao Quang
%A Gewirtz, Andrew T
%A Stepien, Magdalena
%A Trichopoulou, Antonia
%A Aleksandrova, Krasimira
%A Olsen, Anja
%A Tjønneland, Anne
%A Overvad, Kim
%A Carbonnel, Franck
%A Boutron-Ruault, Marie-Christine
%A Severi, Gianluca
%A Kühn, Tilman
%A Kaaks, Rudolf
%A Boeing, Heiner
%A Bamia, Christina
%A Lagiou, Pagona
%A Grioni, Sara
%A Panico, Salvatore
%A Palli, Domenico
%A Tumino, Rosario
%A Naccarati, Alessio
%A Peeters, Petra H
%A Bueno-de-Mesquita, H B
%A Weiderpass, Elisabete
%A Castaño, José María Huerta
%A Barricarte, Aurelio
%A Sanchez-Perez, Maria-Jose
%A Dorronsoro, Miren
%A Quirós, J Ramón
%A Agudo, Antonio
%A Sjöberg, Klas
%A Ohlsson, Bodil
%A Hemmingsson, Oskar
%A Werner, Mårten
%A Bradbury, Kathryn E
%A Khaw, Kay-Tee
%A Wareham, Nick
%A Tsilidis, Konstantinos K
%A Aune, Dagfinn
%A Scalbert, Augustin
%A Romieu, Isabelle
%A Riboli, Elio
%A Jenab, Mazda
%T Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study.
%D 2017
%U http://hdl.handle.net/10668/11045
%X Leakage of bacterial products across the gut barrier may play a role in liver diseases which often precede the development of liver cancer. However, human studies, particularly from prospective settings, are lacking. We used a case-control study design nested within a large prospective cohort to assess the association between circulating levels of anti-lipopolysaccharide (LPS) and anti-flagellin immunoglobulin A (IgA) and G (IgG) (reflecting long-term exposures to LPS and flagellin, respectively) and risk of hepatocellular carcinoma. A total of 139 men and women diagnosed with hepatocellular carcinoma between 1992 and 2010 were matched to 139 control subjects. Multivariable rate ratios (RRs), including adjustment for potential confounders, hepatitis B/C positivity, and degree of liver dysfunction, were calculated with conditional logistic regression. Antibody response to LPS and flagellin was associated with a statistically significant increase in the risk of hepatocellular carcinoma (highest vs. lowest quartile: RR = 11.76, 95% confidence interval = 1.70-81.40; P trend = 0.021). This finding did not vary substantially by time from enrollment to diagnosis, and did not change after adjustment for chronic infection with hepatitis B and C viruses. These novel findings, based on exposures up to several years prior to diagnosis, support a role for gut-derived bacterial products in hepatocellular carcinoma development. Further study into the role of gut barrier failure and exposure to bacterial products in liver diseases is warranted.
%K Endotoxins
%K Flagellin
%K Hepatocellular carcinoma
%K Lipopolysaccharide
%K Prospective studies
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