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2. Supplemental Tables S1-S3 from Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Author

Kong, So Yeon, primary, Tran, Hao Quang, primary, Gewirtz, Andrew T., primary, McKeown-Eyssen, Gail, primary, Fedirko, Veronika, primary, Romieu, Isabelle, primary, Tjønneland, Anne, primary, Olsen, Anja, primary, Overvad, Kim, primary, Boutron-Ruault, Marie-Christine, primary, Bastide, Nadia, primary, Affret, Aurélie, primary, Kühn, Tilman, primary, Kaaks, Rudolf, primary, Boeing, Heiner, primary, Aleksandrova, Krasimira, primary, Trichopoulou, Antonia, primary, Kritikou, Maria, primary, Vasilopoulou, Effie, primary, Palli, Domenico, primary, Krogh, Vittorio, primary, Mattiello, Amalia, primary, Tumino, Rosario, primary, Naccarati, Alessio, primary, Bueno-de-Mesquita, H.B., primary, Peeters, Petra H., primary, Weiderpass, Elisabete, primary, Quirós, J. Ramón, primary, Sala, Núria, primary, Sánchez, María-José, primary, Castaño, José María Huerta, primary, Barricarte, Aurelio, primary, Dorronsoro, Miren, primary, Werner, Mårten, primary, Wareham, Nicholas J., primary, Khaw, Kay-Tee, primary, Bradbury, Kathryn E., primary, Freisling, Heinz, primary, Stavropoulou, Faidra, primary, Ferrari, Pietro, primary, Gunter, Marc J., primary, Cross, Amanda J., primary, Riboli, Elio, primary, Bruce, W. Robert, primary, and Jenab, Mazda, primary

Published
2023
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3. Bacterial Translocation and Risk of Liver Cancer in a Finnish Cohort

Author

Yang, Baiyu, primary, Petrick, Jessica L., additional, Thistle, Jake E., additional, Pinto, Ligia A., additional, Kemp, Troy J., additional, Tran, Hao Quang, additional, Gewirtz, Andrew T., additional, Waterboer, Tim, additional, Fedirko, Veronika, additional, Jenab, Mazda, additional, Graubard, Barry I., additional, Weinstein, Stephanie J., additional, Albanes, Demetrius, additional, and McGlynn, Katherine A., additional

Published
2019
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4. Etiology of Diarrhea, Nutritional Outcomes and Novel Intestinal Biomarkers in Tanzanian Infants: A Preliminary Study

Author

Gosselin, Kerri B., Aboud, Said, McDonald, Christine M., Moyo, Sabrina, Khavari, Nasim, Manji, Karim, Kisenge, Rodrick, Fawzi, Wafaie, Kellogg, Mark, Tran, Hao Quang, Kibiki, Gibson, Gratz, Jean, Liu, Jie, Gewirtz, Andrew, Houpt, Eric, and Duggan, Christopher

Subjects
Diarrhea, Lipopolysaccharides, Male, Rotavirus, Body Weight, Cryptosporidium, Infant, Nutritional Status, Campylobacter, Infections, Polymerase Chain Reaction, Tanzania, Article, Gastrointestinal Microbiome, Immunoglobulin A, Intestines, Enteropathogenic Escherichia coli, Feces, Intestinal Diseases, Humans, Female, Shigella, Biomarkers, Growth Disorders, Flagellin
Abstract

Diarrheal diseases are a leading cause of morbidity and mortality worldwide, but the etiology of diarrhea and its relation to nutritional outcomes in resource-limited settings is poorly defined. We sought to determine the etiology of community-acquired diarrhea in Tanzanian infants and to assess the association with anthropometrics and novel intestinal biomarkers.A convenience sample of infants in a trial of zinc and/or multivitamin supplementation in Tanzania was selected. Subjects were enrolled at age 6 weeks and studied for 18 months. Stool samples were obtained from children with acute diarrhea. A novel, polymerase chain reaction-based TaqMan array was used to screen stool for 15 enteropathogens. A subset of subjects had serum gastrointestinal biomarkers measured.One hundred twenty-three subjects with diarrhea were enrolled. The mean ± SD age at stool sample collection was 12.4 ± 3.9 months. Thirty-five enteropathogens were identified in 34 (27.6%) subjects: 11 rotavirus, 9 Cryptosporidium spp, 7 Shigella spp, 3 Campylobacter jejuni/coli, 3 heat stable-enterotoxigenic Escherichia coli, and 2 enteropathogenic E coli. Subjects with any identified enteropathogen had significantly lower weight-for-length z scores (-0.55 ± 1.10 vs 0.03 ± 1.30, P = 0.03) at the final clinic visit than those without an identified pathogen. Fifty of the 123 subjects (40.7%) had serum analyzed for antibodies to lipopolysaccharide (LPS) and flagellin. Subjects with any identified enteropathogen had lower immunoglobulin (IgA) antibodies to LPS (0.75 ± 0.27 vs 1.13 ± 0.77, P = 0.01) and flagellin (0.52 ± 0.16 vs 0.73 ± 0.47, P = 0.02) than those without an identified pathogen.This quantitative polymerase chain reaction method may allow identification of enteropathogens that place children at higher risk for suboptimal growth. IgA anti-LPS and flagellin antibodies hold promise as emerging intestinal biomarkers.

Published
2017

5. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

Author

Fedirko, Veronika, primary, Tran, Hao Quang, additional, Gewirtz, Andrew T., additional, Stepien, Magdalena, additional, Trichopoulou, Antonia, additional, Aleksandrova, Krasimira, additional, Olsen, Anja, additional, Tjønneland, Anne, additional, Overvad, Kim, additional, Carbonnel, Franck, additional, Boutron-Ruault, Marie-Christine, additional, Severi, Gianluca, additional, Kühn, Tilman, additional, Kaaks, Rudolf, additional, Boeing, Heiner, additional, Bamia, Christina, additional, Lagiou, Pagona, additional, Grioni, Sara, additional, Panico, Salvatore, additional, Palli, Domenico, additional, Tumino, Rosario, additional, Naccarati, Alessio, additional, Peeters, Petra H., additional, Bueno-de-Mesquita, H. B., additional, Weiderpass, Elisabete, additional, Castaño, José María Huerta, additional, Barricarte, Aurelio, additional, Sánchez, María-José, additional, Dorronsoro, Miren, additional, Quirós, J. Ramón, additional, Agudo, Antonio, additional, Sjöberg, Klas, additional, Ohlsson, Bodil, additional, Hemmingsson, Oskar, additional, Werner, Mårten, additional, Bradbury, Kathryn E., additional, Khaw, Kay-Tee, additional, Wareham, Nick, additional, Tsilidis, Konstantinos K., additional, Aune, Dagfinn, additional, Scalbert, Augustin, additional, Romieu, Isabelle, additional, Riboli, Elio, additional, and Jenab, Mazda, additional

Published
2017
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6. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma : a nested case-control study

Author

Fedirko, Veronika, Tran, Hao Quang, Gewirtz, Andrew T, Stepien, Magdalena, Trichopoulou, Antonia, Aleksandrova, Krasimira, Olsen, Anja, Tjønneland, Anne, Overvad, Kim, Carbonnel, Franck, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Bamia, Christina, Lagiou, Pagona, Grioni, Sara, Panico, Salvatore, Palli, Domenico, Tumino, Rosario, Naccarati, Alessio, Peeters, Petra H, Bueno-de-Mesquita, H B, Weiderpass, Elisabete, Castaño, José María Huerta, Barricarte, Aurelio, Sánchez, María-José, Dorronsoro, Miren, Quirós, J Ramón, Agudo, Antonio, Sjöberg, Klas, Ohlsson, Bodil, Hemmingsson, Oskar, Werner, Mårten, Bradbury, Kathryn E, Khaw, Kay-Tee, Wareham, Nick, Tsilidis, Konstantinos K, Aune, Dagfinn, Scalbert, Augustin, Romieu, Isabelle, Riboli, Elio, Jenab, Mazda, Fedirko, Veronika, Tran, Hao Quang, Gewirtz, Andrew T, Stepien, Magdalena, Trichopoulou, Antonia, Aleksandrova, Krasimira, Olsen, Anja, Tjønneland, Anne, Overvad, Kim, Carbonnel, Franck, Boutron-Ruault, Marie-Christine, Severi, Gianluca, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Bamia, Christina, Lagiou, Pagona, Grioni, Sara, Panico, Salvatore, Palli, Domenico, Tumino, Rosario, Naccarati, Alessio, Peeters, Petra H, Bueno-de-Mesquita, H B, Weiderpass, Elisabete, Castaño, José María Huerta, Barricarte, Aurelio, Sánchez, María-José, Dorronsoro, Miren, Quirós, J Ramón, Agudo, Antonio, Sjöberg, Klas, Ohlsson, Bodil, Hemmingsson, Oskar, Werner, Mårten, Bradbury, Kathryn E, Khaw, Kay-Tee, Wareham, Nick, Tsilidis, Konstantinos K, Aune, Dagfinn, Scalbert, Augustin, Romieu, Isabelle, Riboli, Elio, and Jenab, Mazda

Abstract

BACKGROUND: 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: = 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.

Published
2017
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7. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: A nested case-control study

Author

Epidemiology & Health Economics, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, MS MDL 1, Fedirko, Veronika, Tran, Hao Quang, Gewirtz, Andrew T., Stepien, Magdalena, Trichopoulou, Antonia, Aleksandrova, Krasimira, Olsen, Anja, Tjønneland, Anne, Overvad, Kim, Carbonnel, Franck, Boutron-Ruault, Marie Christine, Severi, Gianluca, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Bamia, Christina, Lagiou, Pagona, Grioni, Sara, Panico, Salvatore, Palli, Domenico, Tumino, Rosario, Naccarati, Alessio, Peeters, Petra H., Bueno-de-Mesquita, H. B., Weiderpass, Elisabete, Castaño, José María Huerta, Barricarte, Aurelio, Sánchez, María José, Dorronsoro, Miren, Quirós, J. Ramón, Agudo, Antonio, Sjöberg, Klas, Ohlsson, Bodil, Hemmingsson, Oskar, Werner, Mårten, Bradbury, Kathryn E., Khaw, Kay Tee, Wareham, Nick, Tsilidis, Konstantinos K., Aune, Dagfinn, Scalbert, Augustin, Romieu, Isabelle, Riboli, Elio, Jenab, Mazda, Epidemiology & Health Economics, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Cancer, MS MDL 1, Fedirko, Veronika, Tran, Hao Quang, Gewirtz, Andrew T., Stepien, Magdalena, Trichopoulou, Antonia, Aleksandrova, Krasimira, Olsen, Anja, Tjønneland, Anne, Overvad, Kim, Carbonnel, Franck, Boutron-Ruault, Marie Christine, Severi, Gianluca, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Bamia, Christina, Lagiou, Pagona, Grioni, Sara, Panico, Salvatore, Palli, Domenico, Tumino, Rosario, Naccarati, Alessio, Peeters, Petra H., Bueno-de-Mesquita, H. B., Weiderpass, Elisabete, Castaño, José María Huerta, Barricarte, Aurelio, Sánchez, María José, Dorronsoro, Miren, Quirós, J. Ramón, Agudo, Antonio, Sjöberg, Klas, Ohlsson, Bodil, Hemmingsson, Oskar, Werner, Mårten, Bradbury, Kathryn E., Khaw, Kay Tee, Wareham, Nick, Tsilidis, Konstantinos K., Aune, Dagfinn, Scalbert, Augustin, Romieu, Isabelle, Riboli, Elio, and Jenab, Mazda

Published
2017

8. Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Author

Kong, So Yeon, Tran, Hao Quang, Gewirtz, Andrew T., McKeown-Eyssen, Gail, Fedirko, Veronika, Romieu, Isabelle, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bastide, Nadia, Affret, Aurelie, Kuehn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Aleksandrova, Krasimira, Trichopoulou, Antonia, Kritikou, Maria, Vasilopoulou, Effie, Palli, Domenico, Krogh, Vittorio, Mattiello, Amalia, Tumino, Rosario, Naccarati, Alessio, Bueno-de-Mesquita, H. B., Peeters, Petra H., Weiderpass, Elisabete, Ramon Quiros, J., Sala, Nuria, Sanchez, Maria-Jose, Huerta Castano, Jose Maria, Barricarte, Aurelio, Dorronsoro, Miren, Werner, Mårten, Wareham, Nicholas J., Khaw, Kay-Tee, Bradbury, Kathryn E., Freisling, Heinz, Stavropoulou, Faidra, Ferrari, Pietro, Gunter, Marc J., Cross, Amanda J., Riboli, Elio, Bruce, W. Robert, Jenab, Mazda, Kong, So Yeon, Tran, Hao Quang, Gewirtz, Andrew T., McKeown-Eyssen, Gail, Fedirko, Veronika, Romieu, Isabelle, Tjonneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie-Christine, Bastide, Nadia, Affret, Aurelie, Kuehn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Aleksandrova, Krasimira, Trichopoulou, Antonia, Kritikou, Maria, Vasilopoulou, Effie, Palli, Domenico, Krogh, Vittorio, Mattiello, Amalia, Tumino, Rosario, Naccarati, Alessio, Bueno-de-Mesquita, H. B., Peeters, Petra H., Weiderpass, Elisabete, Ramon Quiros, J., Sala, Nuria, Sanchez, Maria-Jose, Huerta Castano, Jose Maria, Barricarte, Aurelio, Dorronsoro, Miren, Werner, Mårten, Wareham, Nicholas J., Khaw, Kay-Tee, Bradbury, Kathryn E., Freisling, Heinz, Stavropoulou, Faidra, Ferrari, Pietro, Gunter, Marc J., Cross, Amanda J., Riboli, Elio, Bruce, W. Robert, and Jenab, Mazda

Abstract

Background: Chronic inflammation and oxidative stress are thought to be involved in colorectal cancer development. These processes may contribute to leakage of bacterial products, such as lipopolysaccharide (LPS) and flagellin, across the gut barrier. The objective of this study, nested within a prospective cohort, was to examine associations between circulating LPS and flagellin serum antibody levels and colorectal cancer risk. Methods: A total of 1,065 incident colorectal cancer cases (colon, n = 667; rectal, n = 398) were matched (1:1) to control subjects. Serum flagellin-and LPS-specific IgA and IgG levels were quantitated by ELISA. Multivariable conditional logistic regression models were used to calculate ORs and 95% confidence intervals (CI), adjusting for multiple relevant confouding factors. Results: Overall, elevated anti-LPS and anti-flagellin biomarker levels were not associated with colorectal cancer risk. After testing potential interactions by various factors relevant for colorectal cancer risk and anti-LPS and anti-flagellin, sex was identified as a statistically significant interaction factor (P-interaction < 0.05 for all the biomarkers). Analyses stratified by sex showed a statistically significant positive colorectal cancer risk association for men (fully-adjusted OR for highest vs. lowest quartile for total anti-LPS + flagellin, 1.66; 95% CI, 1.10-2.51; P-trend, 0.049), whereas a borderline statistically significant inverse association was observed for women (fully-adjusted OR, 0.70; 95% CI, 0.47-1.02; P-trend, 0.18). Conclusion: In this prospective study on European populations, we found bacterial exposure levels to be positively associated to colorectal cancer risk among men, whereas in women, a possible inverse association may exist. Impact: Further studies are warranted to better clarify these preliminary observations. (C) 2016 AACR.

Published
2016
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9. Serum endotoxins and flagellin and risk of colorectal cancer in the European prospective investigation into cancer and nutrition (EPIC) cohort

Author

Infection & Immunity, Cancer, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Kong, So Yeon, Tran, Hao Quang, Gewirtz, Andrew T., McKeown-Eyssen, Gail, Fedirko, Veronika, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie Christine, Bastide, Nadia, Affret, Aurélie, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Aleksandrova, Krasimira, Trichopoulou, Antonia, Kritikou, Maria, Vasilopoulou, Effie, Palli, Domenico, Krogh, Vittorio, Mattiello, Amalia, Tumino, Rosario, Naccarati, Alessio, Bueno-De-mesquita, H. B., Peeters, Petra H., Weiderpass, Elisabete, Quirós, J. Ramón, Sala, Núria, Sánchez, María José, Castanõ, José María Huerta, Barricarte, Aurelio, Dorronsoro, Miren, Werner, Marten, Wareham, Nicholas J., Khaw, Kay Tee, Bradbury, Kathryn E., Freisling, Heinz, Stavropoulou, Faidra, Ferrari, Pietro, Gunter, Marc J., Cross, Amanda J., Riboli, Elio, Bruce, W. Robert, Jenab, Mazda, Infection & Immunity, Cancer, Epi Kanker Team 1, JC onderzoeksprogramma Kanker, Kong, So Yeon, Tran, Hao Quang, Gewirtz, Andrew T., McKeown-Eyssen, Gail, Fedirko, Veronika, Romieu, Isabelle, Tjønneland, Anne, Olsen, Anja, Overvad, Kim, Boutron-Ruault, Marie Christine, Bastide, Nadia, Affret, Aurélie, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Aleksandrova, Krasimira, Trichopoulou, Antonia, Kritikou, Maria, Vasilopoulou, Effie, Palli, Domenico, Krogh, Vittorio, Mattiello, Amalia, Tumino, Rosario, Naccarati, Alessio, Bueno-De-mesquita, H. B., Peeters, Petra H., Weiderpass, Elisabete, Quirós, J. Ramón, Sala, Núria, Sánchez, María José, Castanõ, José María Huerta, Barricarte, Aurelio, Dorronsoro, Miren, Werner, Marten, Wareham, Nicholas J., Khaw, Kay Tee, Bradbury, Kathryn E., Freisling, Heinz, Stavropoulou, Faidra, Ferrari, Pietro, Gunter, Marc J., Cross, Amanda J., Riboli, Elio, Bruce, W. Robert, and Jenab, Mazda

Published
2016

11. Serum Endotoxins and Flagellin and Risk of Colorectal Cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) Cohort

Author

Kong, So Yeon, primary, Tran, Hao Quang, additional, Gewirtz, Andrew T., additional, McKeown-Eyssen, Gail, additional, Fedirko, Veronika, additional, Romieu, Isabelle, additional, Tjønneland, Anne, additional, Olsen, Anja, additional, Overvad, Kim, additional, Boutron-Ruault, Marie-Christine, additional, Bastide, Nadia, additional, Affret, Aurélie, additional, Kühn, Tilman, additional, Kaaks, Rudolf, additional, Boeing, Heiner, additional, Aleksandrova, Krasimira, additional, Trichopoulou, Antonia, additional, Kritikou, Maria, additional, Vasilopoulou, Effie, additional, Palli, Domenico, additional, Krogh, Vittorio, additional, Mattiello, Amalia, additional, Tumino, Rosario, additional, Naccarati, Alessio, additional, Bueno-de-Mesquita, H.B., additional, Peeters, Petra H., additional, Weiderpass, Elisabete, additional, Quirós, J. Ramón, additional, Sala, Núria, additional, Sánchez, María-José, additional, Castaño, José María Huerta, additional, Barricarte, Aurelio, additional, Dorronsoro, Miren, additional, Werner, Mårten, additional, Wareham, Nicholas J., additional, Khaw, Kay-Tee, additional, Bradbury, Kathryn E., additional, Freisling, Heinz, additional, Stavropoulou, Faidra, additional, Ferrari, Pietro, additional, Gunter, Marc J., additional, Cross, Amanda J., additional, Riboli, Elio, additional, Bruce, W. Robert, additional, and Jenab, Mazda, additional

Published
2016
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14. Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study

Author

Augustin Scalbert, Dagfinn Aune, Andrew T. Gewirtz, Mazda Jenab, Veronika Fedirko, Christina Bamia, Nicholas J. Wareham, Elio Riboli, J. Ramón Quirós, Rudolf Kaaks, Aurelio Barricarte, Rosario Tumino, Salvatore Panico, María José Sánchez, Gianluca Severi, Kim Overvad, Antonia Trichopoulou, Sara Grioni, Domenico Palli, H. B. Bueno-De-Mesquita, Antonio Agudo, Isabelle Romieu, Mårten Werner, Tilman Kühn, Elisabete Weiderpass, Oskar Hemmingsson, Kathryn E. Bradbury, Pagona Lagiou, Hao Quang Tran, Marie-Christine Boutron-Ruault, Anne Tjønneland, Alessio Naccarati, José María Huerta Castaño, Franck Carbonnel, Magdalena Stepien, Kay-Tee Khaw, Krasimira Aleksandrova, Bodil Ohlsson, Petra H.M. Peeters, Heiner Boeing, Anja Olsen, Konstantinos K. Tsilidis, Miren Dorronsoro, Klas Sjöberg, Khaw, Kay-Tee [0000-0002-8802-2903], Wareham, Nicholas [0000-0003-1422-2993], Apollo - University of Cambridge Repository, Fedirko, Veronika, Tran, Hao Quang, Gewirtz, Andrew T, Stepien, Magdalena, Trichopoulou, Antonia, Aleksandrova, Krasimira, Olsen, Anja, Tjønneland, Anne, Overvad, Kim, Carbonnel, Franck, Boutron Ruault, Marie Christine, Severi, Gianluca, Kühn, Tilman, Kaaks, Rudolf, Boeing, Heiner, Bamia, Christina, Lagiou, Pagona, Grioni, Sara, Panico, Salvatore, Palli, Domenico, Tumino, Rosario, Naccarati, Alessio, Peeters, Petra H, Bueno de Mesquita, H. B, Weiderpass, Elisabete, Castaño, José María Huerta, Barricarte, Aurelio, Sánchez, María José, Dorronsoro, Miren, Quirós, J. Ramón, Agudo, Antonio, Sjöberg, Kla, Ohlsson, Bodil, Hemmingsson, Oskar, Werner, Mårten, Bradbury, Kathryn E, Khaw, Kay Tee, Wareham, Nick, Tsilidis, Konstantinos K, Aune, Dagfinn, Scalbert, Augustin, Romieu, Isabelle, Riboli, Elio, and Jenab, Mazda

Subjects
Lipopolysaccharides, Male, 0301 basic medicine, Immunoglobulin A, Hepatocellular carcinoma, lcsh:Medicine, Cohort Studies, 0302 clinical medicine, Endotoxin, Risk Factors, Prospective cohort study, RISK, Medicine(all), biology, NONALCOHOLIC STEATOHEPATITIS, GUT MICROBIOTA, Liver Neoplasms, Confounding, 11 Medical And Health Sciences, General Medicine, VDP::Medical disciplines: 700::Health sciences: 800, Middle Aged, Hepatitis B, CANCER, CROHNS-DISEASE, Multicenter Study, VDP::Medisinske Fag: 700::Helsefag: 800, 030220 oncology & carcinogenesis, NUTRITION, Female, Liver cancer, Life Sciences & Biomedicine, Research Article, Adult, DIET-INDUCED OBESITY, Carcinoma, Hepatocellular, Lipopolysaccharide, Càncer de fetge, 03 medical and health sciences, Medicine, General & Internal, SDG 3 - Good Health and Well-being, General & Internal Medicine, Journal Article, medicine, Humans, FATTY LIVER-DISEASE, Aged, Science & Technology, business.industry, lcsh:R, Klinisk medicin, medicine.disease, Endotoxins, 030104 developmental biology, PROSPECTIVE COHORT, Case-Control Studies, Immunoglobulin G, Nested case-control study, Immunology, biology.protein, Clinical Medicine, business, Prospective studies, Flagellin
Abstract

All Author: 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 and Mazda Jenab., Background: 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; Ptrend = 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., This work was supported by the French National Cancer Institute (L’Institut National du Cancer; INCA) (grant number 2009-139; Principal Investigator: M. Jenab). 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 the 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, and Federal Ministry of Education and Research (Germany); the Hellenic Health Foundation (Greece); the Sicilian Government, AIRE ONLUS Ragusa, AVIS Ragusa, Associazione Italiana per la Ricerca sul Cancro-AIRC-Italy, and National Research Council (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); Nordic Centre of Excellence programme on Food, Nutrition and Health. (Norway); Health Research Fund (FIS), PI13/00061 to Granada), Regional Governments of Andalucía, Asturias, Basque Country, Murcia (no. 6236) and Navarra, Regional Government of Asturias (Asturias, Spain), and ISCIII RETIC (RD06/0020) (Spain); Swedish Cancer Society, Swedish Scientific Council, and County Councils of Skåne and Västerbotten (Sweden); Cancer Research UK (14136 to EPIC-Norfolk; C570/A16491 to EPIC-Oxford) and Medical Research Council (1000143 to EPIC-Norfolk) (United Kingdom); and a Girdlers’ New Zealand Health Research Council Fellowship (to Dr. K.E. Bradbury). 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.

Published
2017
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