Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/34877
Title: Intratumoral presence of the genotoxic gut bacteria pks+ E. coli, Enterotoxigenic Bacteroides fragilis, and Fusobacterium nucleatum and their association with clinicopathological and molecular features of colorectal cancer.
Austin Authors: Joo, Jihoon E;Chu, Yen Lin;Georgeson, Peter;Walker, Romy;Mahmood, Khalid;Clendenning, Mark;Meyers, Aaron L;Como, Julia;Joseland, Sharelle;Preston, Susan G;Diepenhorst, Natalie;Toner, Julie;Ingle, Danielle J;Sherry, Norelle L ;Metz, Andrew;Lynch, Brigid M;Milne, Roger L;Southey, Melissa C;Hopper, John L;Win, Aung Ko;Macrae, Finlay A;Winship, Ingrid M;Rosty, Christophe;Jenkins, Mark A;Buchanan, Daniel D
Affiliation: Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia.;University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia.
Department of Microbiology and Immunology, The Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia.
Endoscopy Unit, Department of Gastroenterology and Hepatology, The Royal Melbourne Hospital, Parkville, VIC, Australia.;Melbourne Medical School, The University of Melbourne, Parkville, VIC, Australia.
Infectious Diseases
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.;Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.;Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia.
Cancer Epidemiology Division, Cancer Council Victoria, Melbourne, VIC, Australia.;Precision Medicine, School of Clinical Sciences at Monash Health, Monash University, Melbourne, VIC, Australia.;Department of Clinical Pathology, Melbourne Medical School, The University of Melbourne, Melbourne, VIC, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Colorectal Medicine and Genetics, The Royal Melbourne Hospital, Parkville, VIC, Australia.;Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.
Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.;Department of Medicine, The University of Melbourne, Parkville, VIC, Australia.
Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, VIC, Australia.
Colorectal Oncogenomics Group, Department of Clinical Pathology, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, VIC, Australia.;University of Melbourne Centre for Cancer Research, Victorian Comprehensive Cancer Centre, Parkville, VIC, Australia.;Genomic Medicine and Family Cancer Clinic, Royal Melbourne Hospital, Parkville, Melbourne, VIC, Australia.
Issue Date: Mar-2024
Date: 2024
Publication information: British Journal of Cancer 2024-03; 130(5)
Abstract: This study aimed to investigate clinicopathological and molecular tumour features associated with intratumoral pks+ Escherichia coli (pks+E.coli+), pks+E.coli- (non-E.coli bacteria harbouring the pks island), Enterotoxigenic Bacteroides fragilis (ETBF) and Fusobacterium nucleatum (F. nucleatum). We screened 1697 tumour-derived DNA samples from the Australasian Colorectal Cancer Family Registry, Melbourne Collaborative Cohort Study and the ANGELS study using targeted PCR. Pks+E.coli+ was associated with male sex (P < 0.01) and APC:c.835-8 A > G somatic mutation (P = 0.03). The association between pks+E.coli+ and APC:c.835-8 A > G was specific to early-onset CRCs (diagnosed<45years, P = 0.02). The APC:c.835-A > G was not associated with pks+E.coli- (P = 0.36). F. nucleatum was associated with DNA mismatch repair deficiency (MMRd), BRAF:c.1799T>A p.V600E mutation, CpG island methylator phenotype, proximal tumour location, and high levels of tumour infiltrating lymphocytes (Ps < 0.01). In the stratified analysis by MMRd subgroups, F. nucleatum was associated with Lynch syndrome, MLH1 methylated and double MMR somatic mutated MMRd subgroups (Ps < 0.01). Intratumoral pks+E.coli+ but not pks+E.coli- are associated with CRCs harbouring the APC:c.835-8 A > G somatic mutation, suggesting that this mutation is specifically related to DNA damage from colibactin-producing E.coli exposures. F. nucleatum was associated with both hereditary and sporadic MMRd subtypes, suggesting the MMRd tumour microenvironment is important for F. nucleatum colonisation irrespective of its cause.
URI: https://ahro.austin.org.au/austinjspui/handle/1/34877
DOI: 10.1038/s41416-023-02554-x
ORCID: 0000-0002-5096-4735
0000-0001-8060-547X
0000-0002-2794-5261
0000-0003-4035-9678
0000-0003-2225-6675
Journal: British Journal of Cancer
PubMed URL: 38200234
ISSN: 1532-1827
Type: Journal Article
Appears in Collections:Journal articles

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