Fedirko, VeronikaTran, Hao QuangGewirtz, Andrew T.Stepien, MagdalenaTrichopoulou, AntoniaAleksandrova, KrasimiraOlsen, AnjaTjønneland, AnneOvervad, KimCarbonnel, FranckBoutron-Ruault, Marie-ChristineSeveri, GianlucaKühn, TilmanKaaks, RudolfBoeing, HeinerBamia, ChristinaLagiou, PagonaGrioni, SaraPanico, SalvatorePalli, DomenicoTumino, RosarioNaccarati, AlessioPeeters, Petra H. M.Bueno de Mesquita, H. BasWeiderpass, ElisabeteHuerta Castaño, José MaríaBarricarte, AurelioSánchez, María JoséDorronsoro, MirenQuirós, José RamónAgudo, AntonioSjöberg, KlasOhlsson, BodilHemmingsson, OskarWerner, MårtenBradbury, Kathryn E.Khaw, Kay-TeeWareham, Nicholas J.Tsilidis, Konstantinos K.Aune, DagfinnScalbert, AugustinRomieu, IsabelleRiboli, ElioJenab, Mazda2018-09-102018-09-102017-04-04https://hdl.handle.net/2445/124409Background: 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. Methods: 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. Results: 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. Conclusions: 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.12 p.application/pdfengcc by (c) Fedirko et al., 2017http://creativecommons.org/licenses/by/3.0/es/Càncer de fetgeLiver cancerinfo:eu-repo/semantics/article2018-07-24info:eu-repo/semantics/openAccess28372583