Molecular and Pathology Features of Colorectal Tumors and Patient Outcomes Are Associated with Fusobacterium nucleatum and Its Subspecies animalis .

Autor:	Borozan I; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Zaidi SH; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Harrison TA; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Phipps AI; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Zheng J; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Lee S; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Trinh QM; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Steinfelder RS; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Adams J; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Banbury BL; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Berndt SI; Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland., Brezina S; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Buchanan DD; Colorectal Oncogenomics Group, Department of Clinical Pathology, The University of Melbourne, Parkville, Victoria, Australia.; The University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia.; Familial Cancer Clinic, Genetic Medicine, The Royal Melbourne Hospital, Parkville, Victoria, Australia.; Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia., Bullman S; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, Washington., Cao Y; Division of Public Health Sciences, Department of Surgery, Washington University School of Medicine in St. Louis, St Louis, Missouri.; Siteman Cancer Center, Washington University School of Medicine in St. Louis, St Louis, Missouri., Farris AB 3rd; Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia., Figueiredo JC; Department of Medicine, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California., Giannakis M; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Broad Institute of MIT and Harvard, Cambridge, Massachusetts., Heisler LE; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Hopper JL; The University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, Victoria, Australia., Lin Y; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Luo X; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Nishihara R; Department of Oncologic Pathology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts., Mardis ER; The Steve and Cindy Rasmussen Institute for Genomic Medicine, Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio., Papadopoulos N; Ludwig Center for Cancer Genetics and Therapeutics, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medicine, Baltimore, Maryland., Qu C; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Reid EEG; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Thibodeau SN; Division of Laboratory Genetics, Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota., Harlid S; Oncology, Department of Radiation Sciences, Faculty of Medicine, Umeå University, Umeå, Sweden., Um CY; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia., Hsu L; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington.; Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington., Gsur A; Institute of Cancer Research, Department of Medicine I, Medical University of Vienna, Vienna, Austria., Campbell PT; Behavioral and Epidemiology Research Group, American Cancer Society, Atlanta, Georgia., Gallinger S; Ontario Institute for Cancer Research, Toronto, Ontario, Canada.; Lunenfeld-Tanenbaum Research Institute, Sinai Health, University of Toronto, Toronto, Ontario, Canada.; General Surgery, Surgery and Critical Care Program, University Health Network Toronto General Hospital, University of Toronto, Toronto, Ontario, Canada., Newcomb PA; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington., Ogino S; Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, Massachusetts.; Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts.; Cancer Immunology Program, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts.; Cancer Epidemiology Program, Dana-Farber/Harvard Cancer Center, Boston, Massachusetts., Sun W; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington., Hudson TJ; Ontario Institute for Cancer Research, Toronto, Ontario, Canada., Ferretti V; Ontario Institute for Cancer Research, Toronto, Ontario, Canada. upeters@fredhutch.org vincent.ferretti.hsj@ssss.gouv.qc.ca.; CHU Sainte-Justine Research Center, University of Montreal, Montreal, Quebec, Canada., Peters U; Public Health Sciences Division, Fred Hutchinson Cancer Research Centre, Seattle, Washington. upeters@fredhutch.org vincent.ferretti.hsj@ssss.gouv.qc.ca.; Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington.
Jazyk:	angličtina
Zdroj:	Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology [Cancer Epidemiol Biomarkers Prev] 2022 Jan; Vol. 31 (1), pp. 210-220. Date of Electronic Publication: 2021 Nov 04.
DOI:	10.1158/1055-9965.EPI-21-0463
Abstrakt:	Background: Fusobacterium nucleatum ( F. nucleatum ) activates oncogenic signaling pathways and induces inflammation to promote colorectal carcinogenesis. Methods: We characterized F. nucleatum and its subspecies in colorectal tumors and examined associations with tumor characteristics and colorectal cancer-specific survival. We conducted deep sequencing of nusA , nusG , and bacterial 16s rRNA genes in tumors from 1,994 patients with colorectal cancer and assessed associations between F. nucleatum presence and clinical characteristics, colorectal cancer-specific mortality, and somatic mutations. Results: F. nucleatum , which was present in 10.3% of tumors, was detected in a higher proportion of right-sided and advanced-stage tumors, particularly subspecies animalis . Presence of F. nucleatum was associated with higher colorectal cancer-specific mortality (HR, 1.97; P = 0.0004). This association was restricted to nonhypermutated, microsatellite-stable tumors (HR, 2.13; P = 0.0002) and those who received chemotherapy [HR, 1.92; confidence interval (CI), 1.07-3.45; P = 0.029). Only F. nucleatum subspecies animalis , the main subspecies detected (65.8%), was associated with colorectal cancer-specific mortality (HR, 2.16; P = 0.0016), subspecies vincentii and nucleatum were not (HR, 1.07; P = 0.86). Additional adjustment for tumor stage suggests that the effect of F. nucleatum on mortality is partly driven by a stage shift. Presence of F. nucleatum was associated with microsatellite instable tumors, tumors with POLE exonuclease domain mutations, and ERBB3 mutations, and suggestively associated with TP53 mutations. Conclusions: F. nucleatum , and particularly subspecies animalis , was associated with a higher colorectal cancer-specific mortality and specific somatic mutated genes. Impact: Our findings identify the F. nucleatum subspecies animalis as negatively impacting colorectal cancer mortality, which may occur through a stage shift and its effect on chemoresistance. (©2021 American Association for Cancer Research.)
Databáze:	MEDLINE
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