Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study
Identifieur interne : 000C47 ( Main/Exploration ); précédent : 000C46; suivant : 000C48Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study
Auteurs : Veronika Fedirko [États-Unis] ; Hao Quang Tran [États-Unis] ; Andrew T. Gewirtz [États-Unis] ; Magdalena Stepien [France] ; Antonia Trichopoulou [Grèce] ; Krasimira Aleksandrova [Allemagne] ; Anja Olsen [Danemark] ; Anne Tj Nneland [Danemark] ; Kim Overvad [Danemark] ; Franck Carbonnel [France] ; Marie-Christine Boutron-Ruault [France] ; Gianluca Severi [France, Italie, Australie] ; Tilman Kühn [Allemagne] ; Rudolf Kaaks [Allemagne] ; Heiner Boeing [Allemagne] ; Christina Bamia [Grèce] ; Pagona Lagiou [Grèce, États-Unis] ; Sara Grioni [Italie] ; Salvatore Panico [Italie] ; Domenico Palli [Italie] ; Rosario Tumino [Italie] ; Alessio Naccarati [Italie] ; Petra H. Peeters [Pays-Bas] ; H. B. Bueno-De-Mesquita [Pays-Bas, Royaume-Uni, Malaisie] ; Elisabete Weiderpass [Norvège, Suède, Finlande] ; José María Huerta Casta O [Espagne] ; Aurelio Barricarte [Espagne] ; María-José Sánchez [Espagne] ; Miren Dorronsoro [Espagne] ; J. Ram N Quir S [Espagne] ; Antonio Agudo [Espagne] ; Klas Sjöberg [Suède] ; Bodil Ohlsson [Suède] ; Oskar Hemmingsson [Suède] ; M Rten Werner [Suède] ; Kathryn E. Bradbury [Royaume-Uni] ; Kay-Tee Khaw [Royaume-Uni] ; Nick Wareham [Royaume-Uni] ; Konstantinos K. Tsilidis [Grèce, Royaume-Uni] ; Dagfinn Aune [Royaume-Uni] ; Augustin Scalbert [France] ; Isabelle Romieu [France] ; Elio Riboli [Royaume-Uni] ; Mazda Jenab [France]Source :
- BMC Medicine [ 1741-7015 ] ; 2017.
Descripteurs français
- KwdFr :
- Adulte, Adulte d'âge moyen, Carcinome hépatocellulaire (immunologie), Carcinome hépatocellulaire (microbiologie), Carcinome hépatocellulaire (sang), Facteurs de risque, Femelle, Flagelline (immunologie), Humains, Immunoglobuline A (immunologie), Immunoglobuline A (sang), Immunoglobuline G (immunologie), Immunoglobuline G (sang), Lipopolysaccharides (immunologie), Mâle, Sujet âgé, Tumeurs du foie (immunologie), Tumeurs du foie (microbiologie), Tumeurs du foie (sang), Études cas-témoins, Études de cohortes, Études prospectives.
- MESH :
- immunologie : Carcinome hépatocellulaire, Flagelline, Immunoglobuline A, Immunoglobuline G, Lipopolysaccharides, Tumeurs du foie.
- microbiologie : Carcinome hépatocellulaire, Tumeurs du foie.
- sang : Carcinome hépatocellulaire, Immunoglobuline A, Immunoglobuline G, Tumeurs du foie.
- Adulte, Adulte d'âge moyen, Facteurs de risque, Femelle, Humains, Mâle, Sujet âgé, Études cas-témoins, Études de cohortes, Études prospectives.
English descriptors
- KwdEn :
- Adult, Aged, Carcinoma, Hepatocellular (blood), Carcinoma, Hepatocellular (immunology), Carcinoma, Hepatocellular (microbiology), Case-Control Studies, Cohort Studies, Female, Flagellin (immunology), Humans, Immunoglobulin A (blood), Immunoglobulin A (immunology), Immunoglobulin G (blood), Immunoglobulin G (immunology), Lipopolysaccharides (immunology), Liver Neoplasms (blood), Liver Neoplasms (immunology), Liver Neoplasms (microbiology), Male, Middle Aged, Prospective Studies, Risk Factors.
- MESH :
- chemical , blood : Immunoglobulin A, Immunoglobulin G.
- chemical , immunology : Flagellin, Immunoglobulin A, Immunoglobulin G, Lipopolysaccharides.
- blood : Carcinoma, Hepatocellular, Liver Neoplasms.
- immunology : Carcinoma, Hepatocellular, Liver Neoplasms.
- microbiology : Carcinoma, Hepatocellular, Liver Neoplasms.
- Adult, Aged, Case-Control Studies, Cohort Studies, Female, Humans, Male, Middle Aged, Prospective Studies, Risk Factors.
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;
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.
The online version of this article (doi:10.1186/s12916-017-0830-8) contains supplementary material, which is available to authorized users.
Url:
DOI: 10.1186/s12916-017-0830-8
PubMed: 28372583
PubMed Central: 5379669
Affiliations:
- Allemagne, Australie, Danemark, Espagne, Finlande, France, Grèce, Italie, Malaisie, Norvège, Pays-Bas, Royaume-Uni, Suède, États-Unis
- Géorgie (États-Unis), Massachusetts
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Le document en format XML
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Athens, Greece</nlm:aff>
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<author><name sortKey="Grioni, Sara" sort="Grioni, Sara" uniqKey="Grioni S" first="Sara" last="Grioni">Sara Grioni</name>
<affiliation wicri:level="1"><nlm:aff id="Aff18">Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, 1 20133 Milano, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, 1 20133 Milano</wicri:regionArea>
<wicri:noRegion>1 20133 Milano</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Panico, Salvatore" sort="Panico, Salvatore" uniqKey="Panico S" first="Salvatore" last="Panico">Salvatore Panico</name>
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<institution-id institution-id-type="GRID">grid.4691.a</institution-id>
<institution></institution>
<institution>Dipartimento di Medicina Clinica Echirurgia Federico II University,</institution>
</institution-wrap>
Naples, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Naples</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Palli, Domenico" sort="Palli, Domenico" uniqKey="Palli D" first="Domenico" last="Palli">Domenico Palli</name>
<affiliation wicri:level="1"><nlm:aff id="Aff20"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1758 0566</institution-id>
<institution-id institution-id-type="GRID">grid.417623.5</institution-id>
<institution></institution>
<institution>Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO,</institution>
</institution-wrap>
Florence, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Florence</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tumino, Rosario" sort="Tumino, Rosario" uniqKey="Tumino R" first="Rosario" last="Tumino">Rosario Tumino</name>
<affiliation wicri:level="1"><nlm:aff id="Aff21">Cancer Registry and Histopathology Unit, “Civic -M.P. Arezzo” Hospital, ASP, Ragusa, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Cancer Registry and Histopathology Unit, “Civic -M.P. Arezzo” Hospital, ASP, Ragusa</wicri:regionArea>
<wicri:noRegion>Ragusa</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name>
<affiliation wicri:level="1"><nlm:aff id="Aff22"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1784 6598</institution-id>
<institution-id institution-id-type="GRID">grid.428948.b</institution-id>
<institution></institution>
<institution>Molecular and Genetic Epidemiology Unit, HuGeF, Human Genetics Foundation,</institution>
</institution-wrap>
Torino, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Torino</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Peeters, Petra H" sort="Peeters, Petra H" uniqKey="Peeters P" first="Petra H." last="Peeters">Petra H. Peeters</name>
<affiliation wicri:level="1"><nlm:aff id="Aff23"><institution-wrap><institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution>Department of Epidemiology, Julius Center for Health Sciences and Primary Care,</institution>
<institution>University Medical Center Utrecht,</institution>
</institution-wrap>
Utrecht, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
<wicri:regionArea>Utrecht</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bueno De Mesquita, H B" sort="Bueno De Mesquita, H B" uniqKey="Bueno De Mesquita H" first="H. B." last="Bueno-De-Mesquita">H. B. Bueno-De-Mesquita</name>
<affiliation wicri:level="1"><nlm:aff id="Aff24"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2208 0118</institution-id>
<institution-id institution-id-type="GRID">grid.31147.30</institution-id>
<institution>Department for Determinants of Chronic Diseases (DCD),</institution>
<institution>National Institute for Public Health and the Environment (RIVM),</institution>
</institution-wrap>
Bilthoven, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Bilthoven</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff25"><institution-wrap><institution-id institution-id-type="ISNI">0000000090126352</institution-id>
<institution-id institution-id-type="GRID">grid.7692.a</institution-id>
<institution>Department of Gastroenterology and Hepatology,</institution>
<institution>University Medical Centre,</institution>
</institution-wrap>
Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Utrecht</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff26"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id>
<institution-id institution-id-type="GRID">grid.7445.2</institution-id>
<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>The School of Public Health, Imperial College London,</institution>
</institution-wrap>
London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>London</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff27"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2308 5949</institution-id>
<institution-id institution-id-type="GRID">grid.10347.31</institution-id>
<institution>Department of Social & Preventive Medicine, Faculty of Medicine,</institution>
<institution>University of Malaya,</institution>
</institution-wrap>
Kuala Lumpur, Malaysia</nlm:aff>
<country xml:lang="fr">Malaisie</country>
<wicri:regionArea>Kuala Lumpur</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Weiderpass, Elisabete" sort="Weiderpass, Elisabete" uniqKey="Weiderpass E" first="Elisabete" last="Weiderpass">Elisabete Weiderpass</name>
<affiliation wicri:level="1"><nlm:aff id="Aff28"><institution-wrap><institution-id institution-id-type="ISNI">0000000122595234</institution-id>
<institution-id institution-id-type="GRID">grid.10919.30</institution-id>
<institution>Department of Community Medicine, Faculty of Health Sciences, University of Tromsø,</institution>
<institution>The Arctic University of Norway,</institution>
</institution-wrap>
Tromsø, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Tromsø</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff29"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0727 140X</institution-id>
<institution-id institution-id-type="GRID">grid.418941.1</institution-id>
<institution>Department of Research, Cancer Registry of Norway,</institution>
<institution>Institute of Population-Based Cancer Research,</institution>
</institution-wrap>
Oslo, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Oslo</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff30"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0626</institution-id>
<institution-id institution-id-type="GRID">grid.4714.6</institution-id>
<institution>Department of Medical Epidemiology and Biostatistics,</institution>
<institution>Karolinska Institutet,</institution>
</institution-wrap>
Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Stockholm</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff31"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0409 6302</institution-id>
<institution-id institution-id-type="GRID">grid.428673.c</institution-id>
<institution></institution>
<institution>Genetic Epidemiology Group, Folkhälsan Research Center,</institution>
</institution-wrap>
Helsinki, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Helsinki</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Casta O, Jose Maria Huerta" sort="Casta O, Jose Maria Huerta" uniqKey="Casta O J" first="José María Huerta" last="Casta O">José María Huerta Casta O</name>
<affiliation wicri:level="1"><nlm:aff id="Aff32"><institution-wrap><institution-id institution-id-type="GRID">grid.452553.0</institution-id>
<institution>Department of Epidemiology,</institution>
<institution>Murcia Regional Health Council, IMIB-Arrixaca,</institution>
</institution-wrap>
Murcia, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Murcia</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff33"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9314 1427</institution-id>
<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Barricarte, Aurelio" sort="Barricarte, Aurelio" uniqKey="Barricarte A" first="Aurelio" last="Barricarte">Aurelio Barricarte</name>
<affiliation wicri:level="1"><nlm:aff id="Aff33"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9314 1427</institution-id>
<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff34">Navarra Public Health Institute, Pamplona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Navarra Public Health Institute, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff35">Navarra Institute for Health Research (IdiSNA), Pamplona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Navarra Institute for Health Research (IdiSNA), Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sanchez, Maria Jose" sort="Sanchez, Maria Jose" uniqKey="Sanchez M" first="María-José" last="Sánchez">María-José Sánchez</name>
<affiliation wicri:level="1"><nlm:aff id="Aff33"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9314 1427</institution-id>
<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff36"><institution-wrap><institution-id institution-id-type="ISNI">0000000121678994</institution-id>
<institution-id institution-id-type="GRID">grid.4489.1</institution-id>
<institution></institution>
<institution>Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada, Universidad de Granada,</institution>
</institution-wrap>
Granada, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Granada</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dorronsoro, Miren" sort="Dorronsoro, Miren" uniqKey="Dorronsoro M" first="Miren" last="Dorronsoro">Miren Dorronsoro</name>
<affiliation wicri:level="1"><nlm:aff id="Aff33"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9314 1427</institution-id>
<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff37">Basque Regional Health Department, San Sebastian, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Basque Regional Health Department, San Sebastian</wicri:regionArea>
<wicri:noRegion>San Sebastian</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Quir S, J Ram N" sort="Quir S, J Ram N" uniqKey="Quir S J" first="J. Ram N" last="Quir S">J. Ram N Quir S</name>
<affiliation wicri:level="1"><nlm:aff id="Aff38">Public Health Directorate, Asturias, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Public Health Directorate, Asturias</wicri:regionArea>
<wicri:noRegion>Asturias</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Agudo, Antonio" sort="Agudo, Antonio" uniqKey="Agudo A" first="Antonio" last="Agudo">Antonio Agudo</name>
<affiliation wicri:level="1"><nlm:aff id="Aff39"><institution-wrap><institution-id institution-id-type="GRID">grid.417656.7</institution-id>
<institution></institution>
<institution>Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat,</institution>
</institution-wrap>
Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sjoberg, Klas" sort="Sjoberg, Klas" uniqKey="Sjoberg K" first="Klas" last="Sjöberg">Klas Sjöberg</name>
<affiliation wicri:level="1"><nlm:aff id="Aff40"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0930 2361</institution-id>
<institution-id institution-id-type="GRID">grid.4514.4</institution-id>
<institution>Department of Clinical Sciences,</institution>
<institution>Lund University,</institution>
</institution-wrap>
Malmö, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Malmö</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff41"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0623 9987</institution-id>
<institution-id institution-id-type="GRID">grid.412650.4</institution-id>
<institution>Department of Gastroenterology and Nutrition,</institution>
<institution>Skåne University Hospital,</institution>
</institution-wrap>
Malmö, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Malmö</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ohlsson, Bodil" sort="Ohlsson, Bodil" uniqKey="Ohlsson B" first="Bodil" last="Ohlsson">Bodil Ohlsson</name>
<affiliation wicri:level="1"><nlm:aff id="Aff42">Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Malmö, Lund University, Lund, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Malmö, Lund University, Lund</wicri:regionArea>
<wicri:noRegion>Lund</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hemmingsson, Oskar" sort="Hemmingsson, Oskar" uniqKey="Hemmingsson O" first="Oskar" last="Hemmingsson">Oskar Hemmingsson</name>
<affiliation wicri:level="1"><nlm:aff id="Aff43"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0623 991X</institution-id>
<institution-id institution-id-type="GRID">grid.412215.1</institution-id>
<institution>Department of Surgical and Perioperative Sciences, Kirurgcentrum,</institution>
<institution>Norrlands Universitetssjukhus,</institution>
</institution-wrap>
Umeå, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Umeå</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Werner, M Rten" sort="Werner, M Rten" uniqKey="Werner M" first="M Rten" last="Werner">M Rten Werner</name>
<affiliation wicri:level="1"><nlm:aff id="Aff44"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0623 991X</institution-id>
<institution-id institution-id-type="GRID">grid.412215.1</institution-id>
<institution>Department of Medicine Sections for Hepatology and Gastroenterology,</institution>
<institution>Umeå University Hospital,</institution>
</institution-wrap>
SE-90185 Umeå, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>SE-90185 Umeå</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bradbury, Kathryn E" sort="Bradbury, Kathryn E" uniqKey="Bradbury K" first="Kathryn E." last="Bradbury">Kathryn E. Bradbury</name>
<affiliation wicri:level="1"><nlm:aff id="Aff45"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8948</institution-id>
<institution-id institution-id-type="GRID">grid.4991.5</institution-id>
<institution>Cancer Epidemiology Unit, Nuffield Department of Population Health,</institution>
<institution>University of Oxford,</institution>
</institution-wrap>
Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Oxford</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name>
<affiliation wicri:level="1"><nlm:aff id="Aff46"><institution-wrap><institution-id institution-id-type="ISNI">0000000121885934</institution-id>
<institution-id institution-id-type="GRID">grid.5335.0</institution-id>
<institution>Clinical Gerontology Unit,</institution>
<institution>University of Cambridge School of Clinical Medicine,</institution>
</institution-wrap>
Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Cambridge</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wareham, Nick" sort="Wareham, Nick" uniqKey="Wareham N" first="Nick" last="Wareham">Nick Wareham</name>
<affiliation wicri:level="1"><nlm:aff id="Aff47"><institution-wrap><institution-id institution-id-type="ISNI">0000000121885934</institution-id>
<institution-id institution-id-type="GRID">grid.5335.0</institution-id>
<institution>MRC Epidemiology Unit,</institution>
<institution>University of Cambridge,</institution>
</institution-wrap>
Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Cambridge</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tsilidis, Konstantinos K" sort="Tsilidis, Konstantinos K" uniqKey="Tsilidis K" first="Konstantinos K." last="Tsilidis">Konstantinos K. Tsilidis</name>
<affiliation wicri:level="1"><nlm:aff id="Aff48"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2108 7481</institution-id>
<institution-id institution-id-type="GRID">grid.9594.1</institution-id>
<institution>Department of Hygiene and Epidemiology,</institution>
<institution>University of Ioannina School of Medicine,</institution>
</institution-wrap>
Ioannina, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Ioannina</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff49"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id>
<institution-id institution-id-type="GRID">grid.7445.2</institution-id>
<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>School of Public Health, Imperial College London,</institution>
</institution-wrap>
London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Aune, Dagfinn" sort="Aune, Dagfinn" uniqKey="Aune D" first="Dagfinn" last="Aune">Dagfinn Aune</name>
<affiliation wicri:level="1"><nlm:aff id="Aff49"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id>
<institution-id institution-id-type="GRID">grid.7445.2</institution-id>
<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>School of Public Health, Imperial College London,</institution>
</institution-wrap>
London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scalbert, Augustin" sort="Scalbert, Augustin" uniqKey="Scalbert A" first="Augustin" last="Scalbert">Augustin Scalbert</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000405980095</institution-id>
<institution-id institution-id-type="GRID">grid.17703.32</institution-id>
<institution></institution>
<institution>Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO),</institution>
</institution-wrap>
Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lyon</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Romieu, Isabelle" sort="Romieu, Isabelle" uniqKey="Romieu I" first="Isabelle" last="Romieu">Isabelle Romieu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000405980095</institution-id>
<institution-id institution-id-type="GRID">grid.17703.32</institution-id>
<institution></institution>
<institution>Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO),</institution>
</institution-wrap>
Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lyon</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Riboli, Elio" sort="Riboli, Elio" uniqKey="Riboli E" first="Elio" last="Riboli">Elio Riboli</name>
<affiliation wicri:level="1"><nlm:aff id="Aff49"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id>
<institution-id institution-id-type="GRID">grid.7445.2</institution-id>
<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>School of Public Health, Imperial College London,</institution>
</institution-wrap>
London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Jenab, Mazda" sort="Jenab, Mazda" uniqKey="Jenab M" first="Mazda" last="Jenab">Mazda Jenab</name>
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Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a" type="main">Exposure to bacterial products lipopolysaccharide and flagellin and hepatocellular carcinoma: a nested case-control study</title>
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Atlanta, GA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
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Atlanta, GA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
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<author><name sortKey="Tran, Hao Quang" sort="Tran, Hao Quang" uniqKey="Tran H" first="Hao Quang" last="Tran">Hao Quang Tran</name>
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<institution>Georgia State University,</institution>
</institution-wrap>
Atlanta, GA 30303 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
</placeName>
<wicri:cityArea>Atlanta</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Gewirtz, Andrew T" sort="Gewirtz, Andrew T" uniqKey="Gewirtz A" first="Andrew T." last="Gewirtz">Andrew T. Gewirtz</name>
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<institution>Georgia State University,</institution>
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Atlanta, GA 30303 USA</nlm:aff>
<country xml:lang="fr">États-Unis</country>
<placeName><region type="state">Géorgie (États-Unis)</region>
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<wicri:cityArea>Atlanta</wicri:cityArea>
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</author>
<author><name sortKey="Stepien, Magdalena" sort="Stepien, Magdalena" uniqKey="Stepien M" first="Magdalena" last="Stepien">Magdalena Stepien</name>
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Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lyon</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Trichopoulou, Antonia" sort="Trichopoulou, Antonia" uniqKey="Trichopoulou A" first="Antonia" last="Trichopoulou">Antonia Trichopoulou</name>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.424637.0</institution-id>
<institution></institution>
<institution>Hellenic Health Foundation,</institution>
</institution-wrap>
13 Kaisareias Street, Athens, GR-115 27 Greece</nlm:aff>
<wicri:noCountry code="subfield">GR-115 27 Greece</wicri:noCountry>
</affiliation>
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<institution-id institution-id-type="GRID">grid.5216.0</institution-id>
<institution>Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health,</institution>
<institution>University of Athens Medical School,</institution>
</institution-wrap>
Athens, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Athens</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Aleksandrova, Krasimira" sort="Aleksandrova, Krasimira" uniqKey="Aleksandrova K" first="Krasimira" last="Aleksandrova">Krasimira Aleksandrova</name>
<affiliation wicri:level="1"><nlm:aff id="Aff7">Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutrition, Immunity and Metabolism Start-up Lab, Nuthetal, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Epidemiology, German Institute of Human Nutrition Potsdam-Rehbruecke, Nutrition, Immunity and Metabolism Start-up Lab, Nuthetal</wicri:regionArea>
<wicri:noRegion>Nuthetal</wicri:noRegion>
<wicri:noRegion>Nuthetal</wicri:noRegion>
<wicri:noRegion>Nuthetal</wicri:noRegion>
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</author>
<author><name sortKey="Olsen, Anja" sort="Olsen, Anja" uniqKey="Olsen A" first="Anja" last="Olsen">Anja Olsen</name>
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<institution-id institution-id-type="GRID">grid.417390.8</institution-id>
<institution></institution>
<institution>Danish Cancer Society Research Center,</institution>
</institution-wrap>
Copenhagen, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Copenhagen</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tj Nneland, Anne" sort="Tj Nneland, Anne" uniqKey="Tj Nneland A" first="Anne" last="Tj Nneland">Anne Tj Nneland</name>
<affiliation wicri:level="1"><nlm:aff id="Aff8"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2175 6024</institution-id>
<institution-id institution-id-type="GRID">grid.417390.8</institution-id>
<institution></institution>
<institution>Danish Cancer Society Research Center,</institution>
</institution-wrap>
Copenhagen, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Copenhagen</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Overvad, Kim" sort="Overvad, Kim" uniqKey="Overvad K" first="Kim" last="Overvad">Kim Overvad</name>
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<institution-id institution-id-type="GRID">grid.7048.b</institution-id>
<institution>Section for Epidemiology, Department of Public Health,</institution>
<institution>Aarhus University,</institution>
</institution-wrap>
Aarhus, Denmark</nlm:aff>
<country xml:lang="fr">Danemark</country>
<wicri:regionArea>Aarhus</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Carbonnel, Franck" sort="Carbonnel, Franck" uniqKey="Carbonnel F" first="Franck" last="Carbonnel">Franck Carbonnel</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10">Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
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<affiliation wicri:level="1"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id>
<institution-id institution-id-type="GRID">grid.14925.3b</institution-id>
<institution></institution>
<institution>Gustave Roussy,</institution>
</institution-wrap>
Villejuif, F-94805 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Villejuif, F-94805 France</wicri:regionArea>
<wicri:noRegion>94805 France</wicri:noRegion>
<wicri:noRegion>94805 France</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff12">Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), University hospitals Paris-Sud, Site de Bicêtre, Paris Sud University, Paris XI, Le Kremlin Bicêtre, Villejuif, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Department of Gastroenterology, Assistance Publique-Hôpitaux de Paris (AP-HP), University hospitals Paris-Sud, Site de Bicêtre, Paris Sud University, Paris XI, Le Kremlin Bicêtre, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Boutron Ruault, Marie Christine" sort="Boutron Ruault, Marie Christine" uniqKey="Boutron Ruault M" first="Marie-Christine" last="Boutron-Ruault">Marie-Christine Boutron-Ruault</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10">Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
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<institution-id institution-id-type="GRID">grid.14925.3b</institution-id>
<institution></institution>
<institution>Gustave Roussy,</institution>
</institution-wrap>
Villejuif, F-94805 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Villejuif, F-94805 France</wicri:regionArea>
<wicri:noRegion>94805 France</wicri:noRegion>
<wicri:noRegion>94805 France</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<affiliation wicri:level="1"><nlm:aff id="Aff10">Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Université Paris-Saclay, Université Paris-Sud, UVSQ, CESP, INSERM, Villejuif</wicri:regionArea>
<wicri:noRegion>Villejuif</wicri:noRegion>
<wicri:noRegion>Villejuif</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff11"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2284 9388</institution-id>
<institution-id institution-id-type="GRID">grid.14925.3b</institution-id>
<institution></institution>
<institution>Gustave Roussy,</institution>
</institution-wrap>
Villejuif, F-94805 France</nlm:aff>
<country wicri:rule="zip">France</country>
<wicri:regionArea>Villejuif, F-94805 France</wicri:regionArea>
<wicri:noRegion>94805 France</wicri:noRegion>
<wicri:noRegion>94805 France</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff13"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1784 6598</institution-id>
<institution-id institution-id-type="GRID">grid.428948.b</institution-id>
<institution></institution>
<institution>Human Genetics Foundation (HuGeF),</institution>
</institution-wrap>
Torino, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Torino</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff14"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 1482 3639</institution-id>
<institution-id institution-id-type="GRID">grid.3263.4</institution-id>
<institution></institution>
<institution>Cancer Council Victoria and University of Melbourne,</institution>
</institution-wrap>
Melbourne, Australia</nlm:aff>
<country xml:lang="fr">Australie</country>
<wicri:regionArea>Melbourne</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kuhn, Tilman" sort="Kuhn, Tilman" uniqKey="Kuhn T" first="Tilman" last="Kühn">Tilman Kühn</name>
<affiliation wicri:level="1"><nlm:aff id="Aff15"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0492 0584</institution-id>
<institution-id institution-id-type="GRID">grid.7497.d</institution-id>
<institution>Division of Cancer Epidemiology,</institution>
<institution>German Cancer Research Center (DKFZ),</institution>
</institution-wrap>
Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Heidelberg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name>
<affiliation wicri:level="1"><nlm:aff id="Aff15"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0492 0584</institution-id>
<institution-id institution-id-type="GRID">grid.7497.d</institution-id>
<institution>Division of Cancer Epidemiology,</institution>
<institution>German Cancer Research Center (DKFZ),</institution>
</institution-wrap>
Heidelberg, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Heidelberg</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Boeing, Heiner" sort="Boeing, Heiner" uniqKey="Boeing H" first="Heiner" last="Boeing">Heiner Boeing</name>
<affiliation wicri:level="1"><nlm:aff id="Aff16"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0390 0098</institution-id>
<institution-id institution-id-type="GRID">grid.418213.d</institution-id>
<institution>Department of Epidemiology,</institution>
<institution>German Institute of Human Nutrition Potsdam-Rehbruecke,</institution>
</institution-wrap>
Nuthetal, Germany</nlm:aff>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Nuthetal</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Bamia, Christina" sort="Bamia, Christina" uniqKey="Bamia C" first="Christina" last="Bamia">Christina Bamia</name>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.424637.0</institution-id>
<institution></institution>
<institution>Hellenic Health Foundation,</institution>
</institution-wrap>
13 Kaisareias Street, Athens, GR-115 27 Greece</nlm:aff>
<wicri:noCountry code="subfield">GR-115 27 Greece</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2155 0800</institution-id>
<institution-id institution-id-type="GRID">grid.5216.0</institution-id>
<institution>Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health,</institution>
<institution>University of Athens Medical School,</institution>
</institution-wrap>
Athens, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Athens</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Lagiou, Pagona" sort="Lagiou, Pagona" uniqKey="Lagiou P" first="Pagona" last="Lagiou">Pagona Lagiou</name>
<affiliation><nlm:aff id="Aff5"><institution-wrap><institution-id institution-id-type="GRID">grid.424637.0</institution-id>
<institution></institution>
<institution>Hellenic Health Foundation,</institution>
</institution-wrap>
13 Kaisareias Street, Athens, GR-115 27 Greece</nlm:aff>
<wicri:noCountry code="subfield">GR-115 27 Greece</wicri:noCountry>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff6"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2155 0800</institution-id>
<institution-id institution-id-type="GRID">grid.5216.0</institution-id>
<institution>Department of Hygiene, Epidemiology and Medical Statistics, WHO Collaborating Center for Nutrition and Health, Unit of Nutritional Epidemiology and Nutrition in Public Health,</institution>
<institution>University of Athens Medical School,</institution>
</institution-wrap>
Athens, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Athens</wicri:regionArea>
</affiliation>
<affiliation wicri:level="2"><nlm:aff id="Aff17"><institution-wrap><institution-id institution-id-type="ISNI">000000041936754X</institution-id>
<institution-id institution-id-type="GRID">grid.38142.3c</institution-id>
<institution>Department of Epidemiology,</institution>
<institution>Harvard School of Public Health,</institution>
</institution-wrap>
Boston, MA USA</nlm:aff>
<country>États-Unis</country>
<placeName><region type="state">Massachusetts</region>
</placeName>
<wicri:cityArea>Boston</wicri:cityArea>
</affiliation>
</author>
<author><name sortKey="Grioni, Sara" sort="Grioni, Sara" uniqKey="Grioni S" first="Sara" last="Grioni">Sara Grioni</name>
<affiliation wicri:level="1"><nlm:aff id="Aff18">Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, 1 20133 Milano, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Epidemiology and Prevention Unit Fondazione IRCCS Istituto Nazionale dei Tumori Via Venezian, 1 20133 Milano</wicri:regionArea>
<wicri:noRegion>1 20133 Milano</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Panico, Salvatore" sort="Panico, Salvatore" uniqKey="Panico S" first="Salvatore" last="Panico">Salvatore Panico</name>
<affiliation wicri:level="1"><nlm:aff id="Aff19"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0790 385X</institution-id>
<institution-id institution-id-type="GRID">grid.4691.a</institution-id>
<institution></institution>
<institution>Dipartimento di Medicina Clinica Echirurgia Federico II University,</institution>
</institution-wrap>
Naples, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Naples</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Palli, Domenico" sort="Palli, Domenico" uniqKey="Palli D" first="Domenico" last="Palli">Domenico Palli</name>
<affiliation wicri:level="1"><nlm:aff id="Aff20"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1758 0566</institution-id>
<institution-id institution-id-type="GRID">grid.417623.5</institution-id>
<institution></institution>
<institution>Molecular and Nutritional Epidemiology Unit, Cancer Research and Prevention Institute – ISPO,</institution>
</institution-wrap>
Florence, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Florence</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tumino, Rosario" sort="Tumino, Rosario" uniqKey="Tumino R" first="Rosario" last="Tumino">Rosario Tumino</name>
<affiliation wicri:level="1"><nlm:aff id="Aff21">Cancer Registry and Histopathology Unit, “Civic -M.P. Arezzo” Hospital, ASP, Ragusa, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Cancer Registry and Histopathology Unit, “Civic -M.P. Arezzo” Hospital, ASP, Ragusa</wicri:regionArea>
<wicri:noRegion>Ragusa</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name>
<affiliation wicri:level="1"><nlm:aff id="Aff22"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1784 6598</institution-id>
<institution-id institution-id-type="GRID">grid.428948.b</institution-id>
<institution></institution>
<institution>Molecular and Genetic Epidemiology Unit, HuGeF, Human Genetics Foundation,</institution>
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Torino, Italy</nlm:aff>
<country xml:lang="fr">Italie</country>
<wicri:regionArea>Torino</wicri:regionArea>
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<author><name sortKey="Peeters, Petra H" sort="Peeters, Petra H" uniqKey="Peeters P" first="Petra H." last="Peeters">Petra H. Peeters</name>
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<institution>Department of Epidemiology, Julius Center for Health Sciences and Primary Care,</institution>
<institution>University Medical Center Utrecht,</institution>
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Utrecht, the Netherlands</nlm:aff>
<country xml:lang="fr" wicri:curation="lc">Pays-Bas</country>
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<author><name sortKey="Bueno De Mesquita, H B" sort="Bueno De Mesquita, H B" uniqKey="Bueno De Mesquita H" first="H. B." last="Bueno-De-Mesquita">H. B. Bueno-De-Mesquita</name>
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<institution>Department for Determinants of Chronic Diseases (DCD),</institution>
<institution>National Institute for Public Health and the Environment (RIVM),</institution>
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Bilthoven, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Bilthoven</wicri:regionArea>
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<institution>Department of Gastroenterology and Hepatology,</institution>
<institution>University Medical Centre,</institution>
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Utrecht, The Netherlands</nlm:aff>
<country xml:lang="fr">Pays-Bas</country>
<wicri:regionArea>Utrecht</wicri:regionArea>
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<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>The School of Public Health, Imperial College London,</institution>
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London, UK</nlm:aff>
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<wicri:regionArea>London</wicri:regionArea>
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<institution>Department of Social & Preventive Medicine, Faculty of Medicine,</institution>
<institution>University of Malaya,</institution>
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Kuala Lumpur, Malaysia</nlm:aff>
<country xml:lang="fr">Malaisie</country>
<wicri:regionArea>Kuala Lumpur</wicri:regionArea>
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</author>
<author><name sortKey="Weiderpass, Elisabete" sort="Weiderpass, Elisabete" uniqKey="Weiderpass E" first="Elisabete" last="Weiderpass">Elisabete Weiderpass</name>
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<institution>Department of Community Medicine, Faculty of Health Sciences, University of Tromsø,</institution>
<institution>The Arctic University of Norway,</institution>
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Tromsø, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Tromsø</wicri:regionArea>
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<institution-id institution-id-type="GRID">grid.418941.1</institution-id>
<institution>Department of Research, Cancer Registry of Norway,</institution>
<institution>Institute of Population-Based Cancer Research,</institution>
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Oslo, Norway</nlm:aff>
<country xml:lang="fr">Norvège</country>
<wicri:regionArea>Oslo</wicri:regionArea>
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<affiliation wicri:level="1"><nlm:aff id="Aff30"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1937 0626</institution-id>
<institution-id institution-id-type="GRID">grid.4714.6</institution-id>
<institution>Department of Medical Epidemiology and Biostatistics,</institution>
<institution>Karolinska Institutet,</institution>
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Stockholm, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Stockholm</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff31"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0409 6302</institution-id>
<institution-id institution-id-type="GRID">grid.428673.c</institution-id>
<institution></institution>
<institution>Genetic Epidemiology Group, Folkhälsan Research Center,</institution>
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Helsinki, Finland</nlm:aff>
<country xml:lang="fr">Finlande</country>
<wicri:regionArea>Helsinki</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Casta O, Jose Maria Huerta" sort="Casta O, Jose Maria Huerta" uniqKey="Casta O J" first="José María Huerta" last="Casta O">José María Huerta Casta O</name>
<affiliation wicri:level="1"><nlm:aff id="Aff32"><institution-wrap><institution-id institution-id-type="GRID">grid.452553.0</institution-id>
<institution>Department of Epidemiology,</institution>
<institution>Murcia Regional Health Council, IMIB-Arrixaca,</institution>
</institution-wrap>
Murcia, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Murcia</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff33"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9314 1427</institution-id>
<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Barricarte, Aurelio" sort="Barricarte, Aurelio" uniqKey="Barricarte A" first="Aurelio" last="Barricarte">Aurelio Barricarte</name>
<affiliation wicri:level="1"><nlm:aff id="Aff33"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9314 1427</institution-id>
<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff34">Navarra Public Health Institute, Pamplona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Navarra Public Health Institute, Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff35">Navarra Institute for Health Research (IdiSNA), Pamplona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Navarra Institute for Health Research (IdiSNA), Pamplona</wicri:regionArea>
<wicri:noRegion>Pamplona</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Sanchez, Maria Jose" sort="Sanchez, Maria Jose" uniqKey="Sanchez M" first="María-José" last="Sánchez">María-José Sánchez</name>
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<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff36"><institution-wrap><institution-id institution-id-type="ISNI">0000000121678994</institution-id>
<institution-id institution-id-type="GRID">grid.4489.1</institution-id>
<institution></institution>
<institution>Escuela Andaluza de Salud Pública. Instituto de Investigación Biosanitaria ibs.GRANADA. Hospitales Universitarios de Granada, Universidad de Granada,</institution>
</institution-wrap>
Granada, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Granada</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Dorronsoro, Miren" sort="Dorronsoro, Miren" uniqKey="Dorronsoro M" first="Miren" last="Dorronsoro">Miren Dorronsoro</name>
<affiliation wicri:level="1"><nlm:aff id="Aff33"><institution-wrap><institution-id institution-id-type="ISNI">0000 0000 9314 1427</institution-id>
<institution-id institution-id-type="GRID">grid.413448.e</institution-id>
<institution></institution>
<institution>CIBER Epidemiología y Salud Pública (CIBERESP),</institution>
</institution-wrap>
Madrid, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Madrid</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff37">Basque Regional Health Department, San Sebastian, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Basque Regional Health Department, San Sebastian</wicri:regionArea>
<wicri:noRegion>San Sebastian</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Quir S, J Ram N" sort="Quir S, J Ram N" uniqKey="Quir S J" first="J. Ram N" last="Quir S">J. Ram N Quir S</name>
<affiliation wicri:level="1"><nlm:aff id="Aff38">Public Health Directorate, Asturias, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Public Health Directorate, Asturias</wicri:regionArea>
<wicri:noRegion>Asturias</wicri:noRegion>
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</author>
<author><name sortKey="Agudo, Antonio" sort="Agudo, Antonio" uniqKey="Agudo A" first="Antonio" last="Agudo">Antonio Agudo</name>
<affiliation wicri:level="1"><nlm:aff id="Aff39"><institution-wrap><institution-id institution-id-type="GRID">grid.417656.7</institution-id>
<institution></institution>
<institution>Unit of Nutrition, Environment and Cancer, Cancer Epidemiology Research Program, Catalan Institute of Oncology-IDIBELL, L’Hospitalet de Llobregat,</institution>
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Barcelona, Spain</nlm:aff>
<country xml:lang="fr">Espagne</country>
<wicri:regionArea>Barcelona</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Sjoberg, Klas" sort="Sjoberg, Klas" uniqKey="Sjoberg K" first="Klas" last="Sjöberg">Klas Sjöberg</name>
<affiliation wicri:level="1"><nlm:aff id="Aff40"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 0930 2361</institution-id>
<institution-id institution-id-type="GRID">grid.4514.4</institution-id>
<institution>Department of Clinical Sciences,</institution>
<institution>Lund University,</institution>
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Malmö, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Malmö</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff41"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0623 9987</institution-id>
<institution-id institution-id-type="GRID">grid.412650.4</institution-id>
<institution>Department of Gastroenterology and Nutrition,</institution>
<institution>Skåne University Hospital,</institution>
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Malmö, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Malmö</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Ohlsson, Bodil" sort="Ohlsson, Bodil" uniqKey="Ohlsson B" first="Bodil" last="Ohlsson">Bodil Ohlsson</name>
<affiliation wicri:level="1"><nlm:aff id="Aff42">Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Malmö, Lund University, Lund, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Department of Clinical Sciences, Division of Internal Medicine, Skåne University Hospital, Malmö, Lund University, Lund</wicri:regionArea>
<wicri:noRegion>Lund</wicri:noRegion>
</affiliation>
</author>
<author><name sortKey="Hemmingsson, Oskar" sort="Hemmingsson, Oskar" uniqKey="Hemmingsson O" first="Oskar" last="Hemmingsson">Oskar Hemmingsson</name>
<affiliation wicri:level="1"><nlm:aff id="Aff43"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0623 991X</institution-id>
<institution-id institution-id-type="GRID">grid.412215.1</institution-id>
<institution>Department of Surgical and Perioperative Sciences, Kirurgcentrum,</institution>
<institution>Norrlands Universitetssjukhus,</institution>
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Umeå, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>Umeå</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Werner, M Rten" sort="Werner, M Rten" uniqKey="Werner M" first="M Rten" last="Werner">M Rten Werner</name>
<affiliation wicri:level="1"><nlm:aff id="Aff44"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 0623 991X</institution-id>
<institution-id institution-id-type="GRID">grid.412215.1</institution-id>
<institution>Department of Medicine Sections for Hepatology and Gastroenterology,</institution>
<institution>Umeå University Hospital,</institution>
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SE-90185 Umeå, Sweden</nlm:aff>
<country xml:lang="fr">Suède</country>
<wicri:regionArea>SE-90185 Umeå</wicri:regionArea>
</affiliation>
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<author><name sortKey="Bradbury, Kathryn E" sort="Bradbury, Kathryn E" uniqKey="Bradbury K" first="Kathryn E." last="Bradbury">Kathryn E. Bradbury</name>
<affiliation wicri:level="1"><nlm:aff id="Aff45"><institution-wrap><institution-id institution-id-type="ISNI">0000 0004 1936 8948</institution-id>
<institution-id institution-id-type="GRID">grid.4991.5</institution-id>
<institution>Cancer Epidemiology Unit, Nuffield Department of Population Health,</institution>
<institution>University of Oxford,</institution>
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Oxford, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Oxford</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name>
<affiliation wicri:level="1"><nlm:aff id="Aff46"><institution-wrap><institution-id institution-id-type="ISNI">0000000121885934</institution-id>
<institution-id institution-id-type="GRID">grid.5335.0</institution-id>
<institution>Clinical Gerontology Unit,</institution>
<institution>University of Cambridge School of Clinical Medicine,</institution>
</institution-wrap>
Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Cambridge</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Wareham, Nick" sort="Wareham, Nick" uniqKey="Wareham N" first="Nick" last="Wareham">Nick Wareham</name>
<affiliation wicri:level="1"><nlm:aff id="Aff47"><institution-wrap><institution-id institution-id-type="ISNI">0000000121885934</institution-id>
<institution-id institution-id-type="GRID">grid.5335.0</institution-id>
<institution>MRC Epidemiology Unit,</institution>
<institution>University of Cambridge,</institution>
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Cambridge, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>Cambridge</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Tsilidis, Konstantinos K" sort="Tsilidis, Konstantinos K" uniqKey="Tsilidis K" first="Konstantinos K." last="Tsilidis">Konstantinos K. Tsilidis</name>
<affiliation wicri:level="1"><nlm:aff id="Aff48"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2108 7481</institution-id>
<institution-id institution-id-type="GRID">grid.9594.1</institution-id>
<institution>Department of Hygiene and Epidemiology,</institution>
<institution>University of Ioannina School of Medicine,</institution>
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Ioannina, Greece</nlm:aff>
<country xml:lang="fr">Grèce</country>
<wicri:regionArea>Ioannina</wicri:regionArea>
</affiliation>
<affiliation wicri:level="1"><nlm:aff id="Aff49"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id>
<institution-id institution-id-type="GRID">grid.7445.2</institution-id>
<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>School of Public Health, Imperial College London,</institution>
</institution-wrap>
London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Aune, Dagfinn" sort="Aune, Dagfinn" uniqKey="Aune D" first="Dagfinn" last="Aune">Dagfinn Aune</name>
<affiliation wicri:level="1"><nlm:aff id="Aff49"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id>
<institution-id institution-id-type="GRID">grid.7445.2</institution-id>
<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>School of Public Health, Imperial College London,</institution>
</institution-wrap>
London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>London</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Scalbert, Augustin" sort="Scalbert, Augustin" uniqKey="Scalbert A" first="Augustin" last="Scalbert">Augustin Scalbert</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000405980095</institution-id>
<institution-id institution-id-type="GRID">grid.17703.32</institution-id>
<institution></institution>
<institution>Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO),</institution>
</institution-wrap>
Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lyon</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Romieu, Isabelle" sort="Romieu, Isabelle" uniqKey="Romieu I" first="Isabelle" last="Romieu">Isabelle Romieu</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000405980095</institution-id>
<institution-id institution-id-type="GRID">grid.17703.32</institution-id>
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<institution>Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO),</institution>
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Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lyon</wicri:regionArea>
</affiliation>
</author>
<author><name sortKey="Riboli, Elio" sort="Riboli, Elio" uniqKey="Riboli E" first="Elio" last="Riboli">Elio Riboli</name>
<affiliation wicri:level="1"><nlm:aff id="Aff49"><institution-wrap><institution-id institution-id-type="ISNI">0000 0001 2113 8111</institution-id>
<institution-id institution-id-type="GRID">grid.7445.2</institution-id>
<institution>Department of Epidemiology and Biostatistics,</institution>
<institution>School of Public Health, Imperial College London,</institution>
</institution-wrap>
London, UK</nlm:aff>
<country xml:lang="fr">Royaume-Uni</country>
<wicri:regionArea>London</wicri:regionArea>
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<author><name sortKey="Jenab, Mazda" sort="Jenab, Mazda" uniqKey="Jenab M" first="Mazda" last="Jenab">Mazda Jenab</name>
<affiliation wicri:level="1"><nlm:aff id="Aff4"><institution-wrap><institution-id institution-id-type="ISNI">0000000405980095</institution-id>
<institution-id institution-id-type="GRID">grid.17703.32</institution-id>
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<institution>Section of Nutrition and Metabolism, International Agency for Research on Cancer (IARC-WHO),</institution>
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Lyon, France</nlm:aff>
<country xml:lang="fr">France</country>
<wicri:regionArea>Lyon</wicri:regionArea>
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</analytic>
<series><title level="j">BMC Medicine</title>
<idno type="eISSN">1741-7015</idno>
<imprint><date when="2017">2017</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Carcinoma, Hepatocellular (blood)</term>
<term>Carcinoma, Hepatocellular (immunology)</term>
<term>Carcinoma, Hepatocellular (microbiology)</term>
<term>Case-Control Studies</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Flagellin (immunology)</term>
<term>Humans</term>
<term>Immunoglobulin A (blood)</term>
<term>Immunoglobulin A (immunology)</term>
<term>Immunoglobulin G (blood)</term>
<term>Immunoglobulin G (immunology)</term>
<term>Lipopolysaccharides (immunology)</term>
<term>Liver Neoplasms (blood)</term>
<term>Liver Neoplasms (immunology)</term>
<term>Liver Neoplasms (microbiology)</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Prospective Studies</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="KwdFr" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Carcinome hépatocellulaire (immunologie)</term>
<term>Carcinome hépatocellulaire (microbiologie)</term>
<term>Carcinome hépatocellulaire (sang)</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Flagelline (immunologie)</term>
<term>Humains</term>
<term>Immunoglobuline A (immunologie)</term>
<term>Immunoglobuline A (sang)</term>
<term>Immunoglobuline G (immunologie)</term>
<term>Immunoglobuline G (sang)</term>
<term>Lipopolysaccharides (immunologie)</term>
<term>Mâle</term>
<term>Sujet âgé</term>
<term>Tumeurs du foie (immunologie)</term>
<term>Tumeurs du foie (microbiologie)</term>
<term>Tumeurs du foie (sang)</term>
<term>Études cas-témoins</term>
<term>Études de cohortes</term>
<term>Études prospectives</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="blood" xml:lang="en"><term>Immunoglobulin A</term>
<term>Immunoglobulin G</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="immunology" xml:lang="en"><term>Flagellin</term>
<term>Immunoglobulin A</term>
<term>Immunoglobulin G</term>
<term>Lipopolysaccharides</term>
</keywords>
<keywords scheme="MESH" qualifier="blood" xml:lang="en"><term>Carcinoma, Hepatocellular</term>
<term>Liver Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="immunologie" xml:lang="fr"><term>Carcinome hépatocellulaire</term>
<term>Flagelline</term>
<term>Immunoglobuline A</term>
<term>Immunoglobuline G</term>
<term>Lipopolysaccharides</term>
<term>Tumeurs du foie</term>
</keywords>
<keywords scheme="MESH" qualifier="immunology" xml:lang="en"><term>Carcinoma, Hepatocellular</term>
<term>Liver Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiologie" xml:lang="fr"><term>Carcinome hépatocellulaire</term>
<term>Tumeurs du foie</term>
</keywords>
<keywords scheme="MESH" qualifier="microbiology" xml:lang="en"><term>Carcinoma, Hepatocellular</term>
<term>Liver Neoplasms</term>
</keywords>
<keywords scheme="MESH" qualifier="sang" xml:lang="fr"><term>Carcinome hépatocellulaire</term>
<term>Immunoglobuline A</term>
<term>Immunoglobuline G</term>
<term>Tumeurs du foie</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Adult</term>
<term>Aged</term>
<term>Case-Control Studies</term>
<term>Cohort Studies</term>
<term>Female</term>
<term>Humans</term>
<term>Male</term>
<term>Middle Aged</term>
<term>Prospective Studies</term>
<term>Risk Factors</term>
</keywords>
<keywords scheme="MESH" xml:lang="fr"><term>Adulte</term>
<term>Adulte d'âge moyen</term>
<term>Facteurs de risque</term>
<term>Femelle</term>
<term>Humains</term>
<term>Mâle</term>
<term>Sujet âgé</term>
<term>Études cas-témoins</term>
<term>Études de cohortes</term>
<term>Études prospectives</term>
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<front><div type="abstract" xml:lang="en"><sec><title>Background</title>
<p>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.</p>
</sec>
<sec><title>Methods</title>
<p>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.</p>
</sec>
<sec><title>Results</title>
<p>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; <italic>P</italic>
<sub>trend</sub>
= 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.</p>
</sec>
<sec><title>Conclusions</title>
<p>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.</p>
</sec>
<sec><title>Electronic supplementary material</title>
<p>The online version of this article (doi:10.1186/s12916-017-0830-8) contains supplementary material, which is available to authorized users.</p>
</sec>
</div>
</front>
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</back>
</TEI>
<affiliations><list><country><li>Allemagne</li>
<li>Australie</li>
<li>Danemark</li>
<li>Espagne</li>
<li>Finlande</li>
<li>France</li>
<li>Grèce</li>
<li>Italie</li>
<li>Malaisie</li>
<li>Norvège</li>
<li>Pays-Bas</li>
<li>Royaume-Uni</li>
<li>Suède</li>
<li>États-Unis</li>
</country>
<region><li>Géorgie (États-Unis)</li>
<li>Massachusetts</li>
</region>
</list>
<tree><country name="États-Unis"><region name="Géorgie (États-Unis)"><name sortKey="Fedirko, Veronika" sort="Fedirko, Veronika" uniqKey="Fedirko V" first="Veronika" last="Fedirko">Veronika Fedirko</name>
</region>
<name sortKey="Fedirko, Veronika" sort="Fedirko, Veronika" uniqKey="Fedirko V" first="Veronika" last="Fedirko">Veronika Fedirko</name>
<name sortKey="Gewirtz, Andrew T" sort="Gewirtz, Andrew T" uniqKey="Gewirtz A" first="Andrew T." last="Gewirtz">Andrew T. Gewirtz</name>
<name sortKey="Lagiou, Pagona" sort="Lagiou, Pagona" uniqKey="Lagiou P" first="Pagona" last="Lagiou">Pagona Lagiou</name>
<name sortKey="Tran, Hao Quang" sort="Tran, Hao Quang" uniqKey="Tran H" first="Hao Quang" last="Tran">Hao Quang Tran</name>
</country>
<country name="France"><noRegion><name sortKey="Stepien, Magdalena" sort="Stepien, Magdalena" uniqKey="Stepien M" first="Magdalena" last="Stepien">Magdalena Stepien</name>
</noRegion>
<name sortKey="Boutron Ruault, Marie Christine" sort="Boutron Ruault, Marie Christine" uniqKey="Boutron Ruault M" first="Marie-Christine" last="Boutron-Ruault">Marie-Christine Boutron-Ruault</name>
<name sortKey="Boutron Ruault, Marie Christine" sort="Boutron Ruault, Marie Christine" uniqKey="Boutron Ruault M" first="Marie-Christine" last="Boutron-Ruault">Marie-Christine Boutron-Ruault</name>
<name sortKey="Carbonnel, Franck" sort="Carbonnel, Franck" uniqKey="Carbonnel F" first="Franck" last="Carbonnel">Franck Carbonnel</name>
<name sortKey="Carbonnel, Franck" sort="Carbonnel, Franck" uniqKey="Carbonnel F" first="Franck" last="Carbonnel">Franck Carbonnel</name>
<name sortKey="Carbonnel, Franck" sort="Carbonnel, Franck" uniqKey="Carbonnel F" first="Franck" last="Carbonnel">Franck Carbonnel</name>
<name sortKey="Jenab, Mazda" sort="Jenab, Mazda" uniqKey="Jenab M" first="Mazda" last="Jenab">Mazda Jenab</name>
<name sortKey="Romieu, Isabelle" sort="Romieu, Isabelle" uniqKey="Romieu I" first="Isabelle" last="Romieu">Isabelle Romieu</name>
<name sortKey="Scalbert, Augustin" sort="Scalbert, Augustin" uniqKey="Scalbert A" first="Augustin" last="Scalbert">Augustin Scalbert</name>
<name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
<name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
</country>
<country name="Grèce"><noRegion><name sortKey="Trichopoulou, Antonia" sort="Trichopoulou, Antonia" uniqKey="Trichopoulou A" first="Antonia" last="Trichopoulou">Antonia Trichopoulou</name>
</noRegion>
<name sortKey="Bamia, Christina" sort="Bamia, Christina" uniqKey="Bamia C" first="Christina" last="Bamia">Christina Bamia</name>
<name sortKey="Lagiou, Pagona" sort="Lagiou, Pagona" uniqKey="Lagiou P" first="Pagona" last="Lagiou">Pagona Lagiou</name>
<name sortKey="Tsilidis, Konstantinos K" sort="Tsilidis, Konstantinos K" uniqKey="Tsilidis K" first="Konstantinos K." last="Tsilidis">Konstantinos K. Tsilidis</name>
</country>
<country name="Allemagne"><noRegion><name sortKey="Aleksandrova, Krasimira" sort="Aleksandrova, Krasimira" uniqKey="Aleksandrova K" first="Krasimira" last="Aleksandrova">Krasimira Aleksandrova</name>
</noRegion>
<name sortKey="Boeing, Heiner" sort="Boeing, Heiner" uniqKey="Boeing H" first="Heiner" last="Boeing">Heiner Boeing</name>
<name sortKey="Kaaks, Rudolf" sort="Kaaks, Rudolf" uniqKey="Kaaks R" first="Rudolf" last="Kaaks">Rudolf Kaaks</name>
<name sortKey="Kuhn, Tilman" sort="Kuhn, Tilman" uniqKey="Kuhn T" first="Tilman" last="Kühn">Tilman Kühn</name>
</country>
<country name="Danemark"><noRegion><name sortKey="Olsen, Anja" sort="Olsen, Anja" uniqKey="Olsen A" first="Anja" last="Olsen">Anja Olsen</name>
</noRegion>
<name sortKey="Overvad, Kim" sort="Overvad, Kim" uniqKey="Overvad K" first="Kim" last="Overvad">Kim Overvad</name>
<name sortKey="Tj Nneland, Anne" sort="Tj Nneland, Anne" uniqKey="Tj Nneland A" first="Anne" last="Tj Nneland">Anne Tj Nneland</name>
</country>
<country name="Italie"><noRegion><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
</noRegion>
<name sortKey="Grioni, Sara" sort="Grioni, Sara" uniqKey="Grioni S" first="Sara" last="Grioni">Sara Grioni</name>
<name sortKey="Naccarati, Alessio" sort="Naccarati, Alessio" uniqKey="Naccarati A" first="Alessio" last="Naccarati">Alessio Naccarati</name>
<name sortKey="Palli, Domenico" sort="Palli, Domenico" uniqKey="Palli D" first="Domenico" last="Palli">Domenico Palli</name>
<name sortKey="Panico, Salvatore" sort="Panico, Salvatore" uniqKey="Panico S" first="Salvatore" last="Panico">Salvatore Panico</name>
<name sortKey="Tumino, Rosario" sort="Tumino, Rosario" uniqKey="Tumino R" first="Rosario" last="Tumino">Rosario Tumino</name>
</country>
<country name="Australie"><noRegion><name sortKey="Severi, Gianluca" sort="Severi, Gianluca" uniqKey="Severi G" first="Gianluca" last="Severi">Gianluca Severi</name>
</noRegion>
</country>
<country name="Pays-Bas"><noRegion><name sortKey="Peeters, Petra H" sort="Peeters, Petra H" uniqKey="Peeters P" first="Petra H." last="Peeters">Petra H. Peeters</name>
</noRegion>
<name sortKey="Bueno De Mesquita, H B" sort="Bueno De Mesquita, H B" uniqKey="Bueno De Mesquita H" first="H. B." last="Bueno-De-Mesquita">H. B. Bueno-De-Mesquita</name>
<name sortKey="Bueno De Mesquita, H B" sort="Bueno De Mesquita, H B" uniqKey="Bueno De Mesquita H" first="H. B." last="Bueno-De-Mesquita">H. B. Bueno-De-Mesquita</name>
</country>
<country name="Royaume-Uni"><noRegion><name sortKey="Bueno De Mesquita, H B" sort="Bueno De Mesquita, H B" uniqKey="Bueno De Mesquita H" first="H. B." last="Bueno-De-Mesquita">H. B. Bueno-De-Mesquita</name>
</noRegion>
<name sortKey="Aune, Dagfinn" sort="Aune, Dagfinn" uniqKey="Aune D" first="Dagfinn" last="Aune">Dagfinn Aune</name>
<name sortKey="Bradbury, Kathryn E" sort="Bradbury, Kathryn E" uniqKey="Bradbury K" first="Kathryn E." last="Bradbury">Kathryn E. Bradbury</name>
<name sortKey="Khaw, Kay Tee" sort="Khaw, Kay Tee" uniqKey="Khaw K" first="Kay-Tee" last="Khaw">Kay-Tee Khaw</name>
<name sortKey="Riboli, Elio" sort="Riboli, Elio" uniqKey="Riboli E" first="Elio" last="Riboli">Elio Riboli</name>
<name sortKey="Tsilidis, Konstantinos K" sort="Tsilidis, Konstantinos K" uniqKey="Tsilidis K" first="Konstantinos K." last="Tsilidis">Konstantinos K. Tsilidis</name>
<name sortKey="Wareham, Nick" sort="Wareham, Nick" uniqKey="Wareham N" first="Nick" last="Wareham">Nick Wareham</name>
</country>
<country name="Malaisie"><noRegion><name sortKey="Bueno De Mesquita, H B" sort="Bueno De Mesquita, H B" uniqKey="Bueno De Mesquita H" first="H. B." last="Bueno-De-Mesquita">H. B. Bueno-De-Mesquita</name>
</noRegion>
</country>
<country name="Norvège"><noRegion><name sortKey="Weiderpass, Elisabete" sort="Weiderpass, Elisabete" uniqKey="Weiderpass E" first="Elisabete" last="Weiderpass">Elisabete Weiderpass</name>
</noRegion>
<name sortKey="Weiderpass, Elisabete" sort="Weiderpass, Elisabete" uniqKey="Weiderpass E" first="Elisabete" last="Weiderpass">Elisabete Weiderpass</name>
</country>
<country name="Suède"><noRegion><name sortKey="Weiderpass, Elisabete" sort="Weiderpass, Elisabete" uniqKey="Weiderpass E" first="Elisabete" last="Weiderpass">Elisabete Weiderpass</name>
</noRegion>
<name sortKey="Hemmingsson, Oskar" sort="Hemmingsson, Oskar" uniqKey="Hemmingsson O" first="Oskar" last="Hemmingsson">Oskar Hemmingsson</name>
<name sortKey="Ohlsson, Bodil" sort="Ohlsson, Bodil" uniqKey="Ohlsson B" first="Bodil" last="Ohlsson">Bodil Ohlsson</name>
<name sortKey="Sjoberg, Klas" sort="Sjoberg, Klas" uniqKey="Sjoberg K" first="Klas" last="Sjöberg">Klas Sjöberg</name>
<name sortKey="Sjoberg, Klas" sort="Sjoberg, Klas" uniqKey="Sjoberg K" first="Klas" last="Sjöberg">Klas Sjöberg</name>
<name sortKey="Werner, M Rten" sort="Werner, M Rten" uniqKey="Werner M" first="M Rten" last="Werner">M Rten Werner</name>
</country>
<country name="Finlande"><noRegion><name sortKey="Weiderpass, Elisabete" sort="Weiderpass, Elisabete" uniqKey="Weiderpass E" first="Elisabete" last="Weiderpass">Elisabete Weiderpass</name>
</noRegion>
</country>
<country name="Espagne"><noRegion><name sortKey="Casta O, Jose Maria Huerta" sort="Casta O, Jose Maria Huerta" uniqKey="Casta O J" first="José María Huerta" last="Casta O">José María Huerta Casta O</name>
</noRegion>
<name sortKey="Agudo, Antonio" sort="Agudo, Antonio" uniqKey="Agudo A" first="Antonio" last="Agudo">Antonio Agudo</name>
<name sortKey="Barricarte, Aurelio" sort="Barricarte, Aurelio" uniqKey="Barricarte A" first="Aurelio" last="Barricarte">Aurelio Barricarte</name>
<name sortKey="Barricarte, Aurelio" sort="Barricarte, Aurelio" uniqKey="Barricarte A" first="Aurelio" last="Barricarte">Aurelio Barricarte</name>
<name sortKey="Barricarte, Aurelio" sort="Barricarte, Aurelio" uniqKey="Barricarte A" first="Aurelio" last="Barricarte">Aurelio Barricarte</name>
<name sortKey="Casta O, Jose Maria Huerta" sort="Casta O, Jose Maria Huerta" uniqKey="Casta O J" first="José María Huerta" last="Casta O">José María Huerta Casta O</name>
<name sortKey="Dorronsoro, Miren" sort="Dorronsoro, Miren" uniqKey="Dorronsoro M" first="Miren" last="Dorronsoro">Miren Dorronsoro</name>
<name sortKey="Dorronsoro, Miren" sort="Dorronsoro, Miren" uniqKey="Dorronsoro M" first="Miren" last="Dorronsoro">Miren Dorronsoro</name>
<name sortKey="Quir S, J Ram N" sort="Quir S, J Ram N" uniqKey="Quir S J" first="J. Ram N" last="Quir S">J. Ram N Quir S</name>
<name sortKey="Sanchez, Maria Jose" sort="Sanchez, Maria Jose" uniqKey="Sanchez M" first="María-José" last="Sánchez">María-José Sánchez</name>
<name sortKey="Sanchez, Maria Jose" sort="Sanchez, Maria Jose" uniqKey="Sanchez M" first="María-José" last="Sánchez">María-José Sánchez</name>
</country>
</tree>
</affiliations>
</record>
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