Dataset Information

Prediagnostic Antibody Responses to Fusobacterium nucleatum Proteins Are Not Associated with Risk of Colorectal Cancer in a Large U.S. Consortium.

ABSTRACT:

Background

The association between prediagnostic antibody responses to Fusobacterium nucleatum (F. nucleatum) and subsequent risk of colorectal cancer is not established.

Methods

We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States.

Results

Higher seroprevalence of any F. nucleatum antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). We did not find any statistically significant association between seropositivity to any of the eight F. nucleatum proteins and colorectal cancer risk.

Conclusions

Prediagnostic antibody responses to F. nucleatum proteins were not associated with the risk of colorectal cancer.

Impact

Future studies may consider a more specific detection of the immunoglobulin isotypes or focus on examining F. nucleatum in stool or tissue samples.

SUBMITTER: Lo CH

PROVIDER: S-EPMC8172443 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Publications

Prediagnostic Antibody Responses to <i>Fusobacterium nucleatum</i> Proteins Are Not Associated with Risk of Colorectal Cancer in a Large U.S. Consortium.

Lo Chun-Han CH Blot William J WJ Teras Lauren R LR Visvanathan Kala K Le Marchand Loïc L Haiman Christopher A CA Chen Yu Y Sesso Howard D HD Wassertheil-Smoller Sylvia S Tinker Lesley F LF Peek Richard M RM Potter John D JD Cover Timothy L TL Zeleniuch-Jacquotte Anne A Berndt Sonja I SI Waterboer Tim T Epplein Meira M Butt Julia J Song Mingyang M

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20210318 6

<h4>Background</h4>The association between prediagnostic antibody responses to <i>Fusobacterium nucleatum</i> (<i>F. nucleatum</i>) and subsequent risk of colorectal cancer is not established.<h4>Methods</h4>We conducted a nested case-control study of 8,126 participants in a consortium of 10 prospective cohorts in the United States.<h4>Results</h4>Higher seroprevalence of any <i>F. nucleatum</i> antibody was observed among non-White participants (51.1%) compared with White participants (31.2%). ...[more]

PMID: 33737297

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Project description:ImportanceEvidence indicates a complex link between gut microbiome, immunity, and intestinal tumorigenesis. To target the microbiota and immunity for colorectal cancer prevention and therapy, a better understanding of the relationship between microorganisms and immune cells in the tumor microenvironment is needed. Experimental evidence suggests that Fusobacterium nucleatum may promote colonic neoplasia development by downregulating antitumor T cell-mediated adaptive immunity.ObjectiveTo test the hypothesis that a greater amount of F nucleatum in colorectal carcinoma tissue is associated with a lower density of T cells in tumor tissue.Design, setting, and participantsA cross-sectional analysis was conducted on 598 rectal and colon carcinoma cases in 2 US nationwide prospective cohort studies with follow-up through 2006, the Nurses' Health Study (participants enrolled in 1976) and the Health Professionals Follow-up Study (participants enrolled in 1986). Tissue collection and processing were performed from 2002 through 2008, and immunity assessment, 2008 through 2009. From 2013 through 2014, the amount of F nucleatum in colorectal carcinoma tissue was measured by quantitative polymerase chain reaction assay; we equally dichotomized positive cases (high vs low). Multivariable ordinal logistic regression analysis was conducted in 2014 to assess associations of the amount of F nucleatum with densities (quartiles) of T cells in tumor tissue, controlling for clinical and tumor molecular features, including microsatellite instability, CpG island methylator phenotype, long interspersed nucleotide element-1 (LINE-1) methylation, and KRAS, BRAF, and PIK3CA mutation status. We adjusted the 2-sided α level to .013 for multiple hypothesis testing.Main outcomes and measuresDensities of CD3+, CD8+, CD45RO (protein tyrosine phosphatase receptor type C [PTPRC])+, and FOXP3+ T cells in tumor tissue, determined by means of tissue microarray immunohistochemical analysis and computer-assisted image analysis.ResultsF nucleatum was detected in colorectal carcinoma tissue in 76 (13%) of 598 cases. Compared with F nucleatum-negative cases, F nucleatum-high cases were inversely associated with the density of CD3+ T cells (for a unit increase in quartile categories of CD3+ T cells as an outcome: multivariable odds ratio, 0.47 [95% CI, 0.26-0.87]; P for trend = .006). The amount of F nucleatum was not significantly associated with the density of CD8+, CD45RO+, or FOXP3+ T cells (P fortrend = .24, .88, and .014, respectively).Conclusions and relevanceThe amount of tissue F nucleatum is inversely associated with CD3+ T-cell density in colorectal carcinoma tissue. On validation, our human population data may provide an impetus for further investigations on potential interactive roles of Fusobacterium and host immunity in colon carcinogenesis.