Evidence map›Paper›PMID 41129365›Full record

ArticleInternational journal of cancer2026

Pre-diagnostic immunological markers of bacterial translocation and liver cancer risk: A nested case-control analysis of 12 prospective cohorts.

Cody Z Watling, Peter T Campbell, Barry I Graubard, Yanyu Wang, Andrew T Gewirtz, Xuehong Zhang, Matthew J Barnett, Julie E Buring, Yu Chen, A Heather Eliassen and 27 more

Abstract read
In one paragraph

Article in International journal of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

37 authors.

Cody Z WatlingDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Peter T CampbellDepartment of Epidemiology & Population Health, Albert Einstein College of Medicine, New York, New York, USA.
Barry I GraubardDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Yanyu WangApplied Developmental Research Directorate, Leidos Biomedical Research Inc, Frederick National Laboratory for Cancer Research, National Cancer Institute, Frederick, Maryland, USA.
Andrew T GewirtzCenter for Inflammation, Immunity and Infection, Institute for Biomedical Sciences, Georgia State University, Atlanta, Georgia, USA.
Xuehong ZhangSchool of Nursing, Yale University, New Haven, Connecticut, USA.
Matthew J BarnettCancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Julie E BuringDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Yu ChenDepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USA.ORCID https://orcid.org/0000-0002-1519-4894
A Heather EliassenDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
J Michael GazianoDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Jonathan N HofmannDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Wen-Yi HuangDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.ORCID https://orcid.org/0000-0002-4440-3368
Jae H KangChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0003-4812-0557
Jill KoshiolDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.ORCID https://orcid.org/0000-0002-3832-6204
Erikka LoftfieldDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
I-Min LeeDivision of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
Steven C MooreDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Lorelei A MucciDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Marian L NeuhouserCancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Christina C NewtonDepartment of Population Science, American Cancer Society, New York, New York, USA.
Mark P PurdueDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.ORCID https://orcid.org/0000-0003-1177-3108
Howard D SessoDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Martha ShrubsoleDivision of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
Rashmi SinhaDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.
Lesley TinkerCancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Matthew TripletteCancer Prevention Program, Division of Public Health Sciences, Fred Hutchinson Cancer Center, Seattle, Washington, USA.
Caroline Y UmDepartment of Population Science, American Cancer Society, New York, New York, USA.
Kala VisvanathanJohns Hopkins School of Medicine and Bloomberg School of Public Health, Baltimore, Maryland, USA.
Eleanor L WattsDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.ORCID https://orcid.org/0000-0001-9229-2589
Jean Wactawski-WendeDepartment of Epidemiology and Environmental Health, University at Buffalo, Buffalo, New York, USA.
Walter WillettDepartment of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
Fen WuDepartment of Population Health, NYU Grossman School of Medicine, New York, New York, USA.
Wei ZhengDivision of Epidemiology, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Nashville, Tennessee, USA.
Dinesh BarupalDepartment of Environmental Medicine, Icahn School of Medicine at Mount Sinai, New York, New York, USA.ORCID https://orcid.org/0000-0002-9954-8628
Jessica L PetrickSlone Epidemiology Center at Boston University, Boston, Massachusetts, USA.ORCID https://orcid.org/0000-0001-6580-450X
Katherine A McGlynnDivision of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, Maryland, USA.ORCID https://orcid.org/0000-0003-2329-9933

Funding

WOMEN'S HEALTH INITIATIVE - CLINICAL COORDINATING CENTER: TASK AREA B - LONG LIFE STUDY VISIT 2 LIMITED HOME VISIT75N92021D00001 · NHLBI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI ANDERSON, GARNET L. · 2021 to 2025
$52.0M
Translational Analysis CoreP30DK058404 · NIDDK · VANDERBILT UNIVERSITY MEDICAL CENTER · PI RICHARD M. PEEK · 2002 to 2026
$29.9M
Women's Health Study: Continued Follow-upR01CA047988 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E., LEE, I-MIN · 1991 to 2014
$28.2M
A Follow-up Study for Causes of Cancer in Black WomenU01CA164974 · NCI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI Kimberly A. Bertrand, Yvette C Cozier · 2017 to 2026
$24.0M
Long Term Multidisciplinary Study of Cancer in Women: The Nurses Health StudyUM1CA186107 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI ELIASSEN, A. HEATHER, STAMPFER, MEIR · 2014 to 2023
$22.3M
Southern Community Cohort StudyU01CA202979 · NCI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI BLOT, WILLIAM J., SHRUBSOLE, MARTHA J. · 2016 to 2025
$22.0M
Physicians' Health Study II: Prevention Trial of VitaminsR01CA097193 · NCI · BRIGHAM AND WOMEN'S HOSPITAL · PI GAZIANO, J. MICHAEL · 2002 to 2011
$15.7M
THE CAROTENE AND RETINOL EFFICACY TRIAL (CARET)U01CA063673 · NCI · FRED HUTCHINSON CANCER RESEARCH CENTER · PI GOODMAN, GARY E · 1994 to 2006
$13.0M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC): TASK AREA A AND A275N92021D00002 · NHLBI · STATE UNIVERSITY OF NEW YORK AT BUFFALO · PI WACTAWSKI-WENDE, JEAN · 2021 to 2025
$6.9M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00004 · NHLBI · STANFORD UNIVERSITY · PI STEFANICK, MARCIA · 2021 to 2025
$6.5M
WOMEN'S HEALTH INITIATIVE (WHI) REGIONAL CENTER (RC) - TO EXERCISE OPTION PERIOD ONE (1) AND REVISE CONTRACT ARTICLES.75N92021D00003 · NHLBI · OHIO STATE UNIVERSITY · PI JACKSON, REBECCA · 2021 to 2025
$5.0M
Women's Health Study: Continued Follow-UpR01HL080467 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI BURING, JULIE E. · 2005 to 2010
$4.5M
American Cancer SocietyCIHR 187861National Institutes of Health IntramuralNCI NIH HHS R01 CA034944NCI NIH HHS R01 CA040360NCI NIH HHS R01 CA047988NCI NIH HHS R01 CA097193NCI NIH HHS U01 CA063673NCI NIH HHS U01 CA164974NCI NIH HHS U01 CA167462NCI NIH HHS U01 CA182913NCI NIH HHS U01 CA202979NCI NIH HHS UM1 CA167462NCI NIH HHS UM1 CA182913NCI NIH HHS UM1 CA186107NHLBI NIH HHS 75N92021D00001NHLBI NIH HHS 75N92021D00002NHLBI NIH HHS R01 HL026490NHLBI NIH HHS R01 HL034595NHLBI NIH HHS R01 HL043851NHLBI NIH HHS R01 HL080467NHLBI NIH HHS RC1 HL099355NIDDK NIH HHS P30 DK058404NIEHS NIH HHS U24 ES035386NIH HHS 75N92021D00001NIH HHS 75N92021D00002NIH HHS 75N92021D00003NIH HHS 75N92021D00004NIH HHS 75N92021D00005NIH HHS CA047988NIH HHS CA097193NIH HHS CA182913NIH HHS CA34944NIH HHS CA40360NIH HHS HL043851NIH HHS HL080467NIH HHS HL09935NIH HHS HL26490NIH HHS HL34595NIH HHS NCI U01 167552NIH HHS U01CA164974NIH HHS U01CA167462NIH HHS U01CA202979NIH HHS U01CA63673NIH HHS U24ES035386NIH HHS UM1CA167462NIH HHS UM1CA186107WHI NIH HHS 75N92021D00003WHI NIH HHS 75N92021D00004WHI NIH HHS 75N92021D00005
6 · The paper itself

Abstract

The gut-liver axis may play an important role in hepatocarcinogenesis. However, limited prospective research has explored associations with liver cancer risk. We conducted a nested case-control study based in 12 prospective cohort studies from across the United States, which included 867 cases of liver cancer and 867 matched controls. We measured bacterial translocation markers, specifically immunoglobulin (Ig) A, IgG, and IgM against lipopolysaccharide and flagellin; soluble CD14 (a co-receptor for lipopolysaccharide); and lipopolysaccharide-binding protein. Multivariable conditional logistic regression was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) between bacterial translocation marker concentrations per doubling in concentrations and liver cancer risk. Lipopolysaccharide-binding protein concentrations were most strongly associated with higher liver cancer risk (OR per doubling in concentrations: 1.48, 95% CI: 1.23-1.79). Concentrations of anti-flagellin IgA (1.13, 1.01-1.28) and IgG (1.13, 1.01-1.28), anti-lipopolysaccharide IgG (1.20, 1.01-1.42), and soluble CD14 (1.12, 1.01-1.24) were also associated with liver cancer risk. When analyses were separated into hepatocellular carcinoma (HCC, N = 436 cases) and intrahepatic cholangiocarcinoma (ICC, N = 110 cases), no evidence of heterogeneity was observed except for lipopolysaccharide-binding protein concentrations, which were positively associated with HCC (1.77, 1.34-2.33) but not ICC (0.67, 0.37-1.22; p-heterogeneity = .003). Associations did not differ by time to liver cancer diagnosis or other subgroups. These findings support the role of gut barrier dysfunction in hepatocarcinogenesis, necessitating further research to understand the complex interplay among the mechanisms and risk factors disrupting the gut barrier, microbiota, and liver cancer.

Indexed as

Bacterial TranslocationLiver NeoplasmsAcute-Phase ProteinsAdultAgedBiomarkers, TumorCarrier ProteinsCase-Control StudiesFemaleFlagellinHumansImmunoglobulin AImmunoglobulin GLipopolysaccharide ReceptorsLipopolysaccharidesMaleAcute-Phase ProteinsBiomarkers, TumorCarrier ProteinsCD14 protein, humanFlagellinImmunoglobulin AImmunoglobulin GLipopolysaccharide ReceptorsLipopolysaccharidesMembrane Glycoproteinsendotoxinflagellingut dysbiosishepatocellular carcinomaintrahepatic cholangiocarcinoma

Identifiers

PMID41129365
PMCPMC12875164

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.