title: Fusobacterium nucleatum in colorectal carcinoma tissue and patient prognosis.
abstract: 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.
  
  
  
  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).
  
  
  
  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.
  
  
  
  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.
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors: Kosuke
authors: K
authors: Mima
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors: Reiko
authors: R
authors: Nishihara
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors: Zhi Rong
authors: ZR
authors: Qian
authors: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors: Yin
authors: Y
authors: Cao
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors: Yasutaka
authors: Y
authors: Sukawa
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Jonathan A
authors: JA
authors: Nowak
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|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.
authors: Juhong
authors: J
authors: Yang
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors: Ruoxu
authors: R
authors: Dou
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors: Yohei
authors: Y
authors: Masugi
authors: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors: Mingyang
authors: M
authors: Song
authors: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.|Center for Computational and Integrative Biology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Aleksandar D
authors: AD
authors: Kostic
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Marios
authors: M
authors: Giannakis
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors: Susan
authors: S
authors: Bullman
authors: Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors: Danny A
authors: DA
authors: Milner
authors: Department of Gastroenterological Surgery, Graduate School of Medical Science, Kumamoto University, Kumamoto, Japan.
authors: Hideo
authors: H
authors: Baba
authors: Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Edward L
authors: EL
authors: Giovannucci
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Levi A
authors: LA
authors: Garraway
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Gordon J
authors: GJ
authors: Freeman
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Cancer Vaccine Center, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors: Glenn
authors: G
authors: Dranoff
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.|Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.
authors: Wendy S
authors: WS
authors: Garrett
authors: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.|Center for the Study of Inflammatory Bowel Disease, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Curtis
authors: C
authors: Huttenhower
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Broad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
authors: Matthew
authors: M
authors: Meyerson
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.
authors: Jeffrey A
authors: JA
authors: Meyerhardt
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.|Division of Gastroenterology, Massachusetts General Hospital, Boston, Massachusetts, USA.
authors: Andrew T
authors: AT
authors: Chan
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Charles S
authors: CS
authors: Fuchs
authors: Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts, USA.|Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts, USA.|Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Shuji
authors: S
authors: Ogino
mesh_terms: D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000382:microbiology* / Q000401:mortality / Q000473:pathology; D016208:Databases, Factual; D005260:Female; D005500:Follow-Up Studies; D016967:Fusobacterium nucleatum / Q000235:genetics / Q000472:pathogenicity*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D053842:Microsatellite Instability; D008875:Middle Aged; D009154:Mutation; D009367:Neoplasm Staging; D010641:Phenotype; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D011446:Prospective Studies; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D012107:Research Design
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras)
keywords: CANCER EPIDEMIOLOGY; COLONIC BACTERIA; COLONIC MICROFLORA; COLORECTAL CANCER; INTESTINAL BACTERIA