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Gut. 2016 Dec;65(12):1973-1980. doi: 10.1136/gutjnl-2015-310101. Epub 2015 Aug 26.

Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis.

Author information

1
Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
2
Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
3
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
4
Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
5
Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
6
Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development, Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, China.
7
Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
8
Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
9
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
10
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
11
Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
12
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
13
Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
14
Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
15
Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

OBJECTIVE:

Accumulating evidence links the intestinal microbiota and colorectal carcinogenesis. Fusobacterium nucleatum may promote colorectal tumour growth and inhibit T cell-mediated immune responses against colorectal tumours. Thus, we hypothesised that the amount of F. nucleatum in colorectal carcinoma might be associated with worse clinical outcome.

DESIGN:

We used molecular pathological epidemiology database of 1069 rectal and colon cancer cases in the Nurses' Health Study and the Health Professionals Follow-up Study, and measured F. nucleatum DNA in carcinoma tissue. Cox proportional hazards model was used to compute hazard ratio (HR), controlling for potential confounders, including microsatellite instability (MSI, mismatch repair deficiency), CpG island methylator phenotype (CIMP), KRAS, BRAF, and PIK3CA mutations, and LINE-1 hypomethylation (low-level methylation).

RESULTS:

Compared with F. nucleatum-negative cases, multivariable HRs (95% CI) for colorectal cancer-specific mortality in F. nucleatum-low cases and F. nucleatum-high cases were 1.25 (0.82 to 1.92) and 1.58 (1.04 to 2.39), respectively, (p for trend=0.020). The amount of F. nucleatum was associated with MSI-high (multivariable odd ratio (OR), 5.22; 95% CI 2.86 to 9.55) independent of CIMP and BRAF mutation status, whereas CIMP and BRAF mutation were associated with F. nucleatum only in univariate analyses (p<0.001) but not in multivariate analysis that adjusted for MSI status.

CONCLUSIONS:

The amount of F. nucleatum DNA in colorectal cancer tissue is associated with shorter survival, and may potentially serve as a prognostic biomarker. Our data may have implications in developing cancer prevention and treatment strategies through targeting GI microflora by diet, probiotics and antibiotics.

KEYWORDS:

CANCER EPIDEMIOLOGY; COLONIC BACTERIA; COLONIC MICROFLORA; COLORECTAL CANCER; INTESTINAL BACTERIA

PMID:
26311717
PMCID:
PMC4769120
DOI:
10.1136/gutjnl-2015-310101
[Indexed for MEDLINE]
Free PMC Article

Conflict of interest statement

Dr. Chan previously served as a consultant for Bayer Healthcare, Millennium Pharmaceuticals, Pozen Inc, and Pfizer Inc. This study was not funded by Bayer Healthcare, Millennium Pharmaceuticals, Pozen Inc, or Pfizer Inc. Dr. Meyerson applies a patent on Fusobacterium in colorectal cancer diagnosis, and has ownership interest in and is a consultant and advisory board member for Foundation Medicine. The other authors declare that they have no competing interests.

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