Title |
Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study
|
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Published in |
BMC Medicine, April 2017
|
DOI | 10.1186/s12916-017-0830-8 |
Pubmed ID | |
Authors |
Veronika Fedirko, Hao Quang Tran, Andrew T. Gewirtz, Magdalena Stepien, Antonia Trichopoulou, Krasimira Aleksandrova, Anja Olsen, Anne Tjønneland, Kim Overvad, Franck Carbonnel, Marie-Christine Boutron-Ruault, Gianluca Severi, Tilman Kühn, Rudolf Kaaks, Heiner Boeing, Christina Bamia, Pagona Lagiou, Sara Grioni, Salvatore Panico, Domenico Palli, Rosario Tumino, Alessio Naccarati, Petra H. Peeters, H. B. Bueno-de-Mesquita, Elisabete Weiderpass, José María Huerta Castaño, Aurelio Barricarte, María-José Sánchez, Miren Dorronsoro, J. Ramón Quirós, Antonio Agudo, Klas Sjöberg, Bodil Ohlsson, Oskar Hemmingsson, Mårten Werner, Kathryn E. Bradbury, Kay-Tee Khaw, Nick Wareham, Konstantinos K. Tsilidis, Dagfinn Aune, Augustin Scalbert, Isabelle Romieu, Elio Riboli, Mazda Jenab |
Abstract |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
Spain | 2 | 22% |
South Africa | 1 | 11% |
United Kingdom | 1 | 11% |
Unknown | 5 | 56% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 6 | 67% |
Scientists | 2 | 22% |
Practitioners (doctors, other healthcare professionals) | 1 | 11% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 75 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Researcher | 10 | 13% |
Student > Master | 7 | 9% |
Student > Doctoral Student | 6 | 8% |
Student > Ph. D. Student | 5 | 7% |
Professor > Associate Professor | 5 | 7% |
Other | 21 | 28% |
Unknown | 21 | 28% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 20 | 27% |
Biochemistry, Genetics and Molecular Biology | 8 | 11% |
Nursing and Health Professions | 7 | 9% |
Agricultural and Biological Sciences | 5 | 7% |
Psychology | 3 | 4% |
Other | 8 | 11% |
Unknown | 24 | 32% |