TOPLINE:
The gut bacteria polyketide synthetase–positive (pks+) Escherichia coli, pks-negative (pks−) E coli, and Fusobacterium nucleatum are enriched in colorectal cancers (CRCs) in patients with Lynch syndrome. Index CRC with pks+ E coli is associated with an increased risk for metachronous CRC and neoplasms.
METHODOLOGY:
- People with Lynch syndrome have an increased risk of developing CRC. Researchers aimed to determine whether the intratumoral presence of three gut bacteria previously linked with CRC is associated with the risk for metachronous CRC in people with Lynch syndrome.
- They assessed the prevalence of those three bacteria — pks+ E coli, F nucleatum, and enterotoxigenic Bacteroides fragilis (ETBF) — as well as pks− E coli in samples from participants with Lynch syndrome identified from the Australasian Colon Cancer Family Registry.
- The analysis involved 386 CRC samples from 316 participants, 90 adenoma samples from 66 participants, and 195 normal colonic mucosa samples from 179 participants, all with Lynch syndrome. A group of 1336 participants who developed sporadic mismatch repair–proficient CRC cases served as a reference group.
- An index CRC was defined as the earliest primary CRC tested for bacteria in cases of metachronous CRC (a new primary CRC diagnosed at least 1 year after a primary CRC diagnosis) or as the case with the most complete data in cases of synchronous CRC (more than one primary CRC diagnosed in the same individual at initial staging).
- Intratumoral presence of bacteria was detected by targeting specific bacterial genes, and its association with molecular and clinicopathologic characteristics and the risk for metachronous CRC and neoplasia were assessed.
TAKEAWAY:
- Compared with sporadic CRCs from the reference group, CRCs from the Lynch syndrome group had a significantly higher prevalence of pks+ E coli (odds ratio [OR], 1.60; P = .017) , pks− E coli (OR, 3.87; P < .001), and F nucleatum (OR, 19.47; P < .001). The prevalence of ETBF was not different between the two groups.
- F nucleatum was significantly less prevalent in adenomas and resection margin normal mucosa than in Lynch syndrome CRCs. The prevalence of pks+ and pks− E coli and ETBF was not significantly different in adenomas or normal mucosa compared with that in CRCs.
- The presence of pks+ E coli in the index CRC was associated with an increased risk for metachronous CRC (hazard ratio [HR], 2.32; P = .005) and metachronous neoplasms (HR, 1.51; P = .04).
- In cases where CRC was positive for pks+ E coli, the bacteria were also present in 100% of the adjacent normal colonic mucosa and 78% of the matched nonadjacent normal colonic mucosa.
IN PRACTICE:
“If these findings are validated, they would have potential clinical implications as pks+ E coli may represent a biomarker to test for in people with LS [Lynch syndrome] to understand their risk of metachronous neoplasms development,” the authors wrote. “People with LS may benefit from the monitoring of pks+ E coli to modulate CRC risks.”
SOURCE:
The study, led by Yen Lin Chu, Victorian Comprehensive Cancer Centre, The University of Melbourne, Parkville, Australia, was published online in eBioMedicine.
LIMITATIONS:
A control group of patients with Lynch syndrome who did not develop CRC was lacking, limiting the understanding of the microbiome’s role before tumorigenesis. Advanced adenomas could not be differentiated from nonadvanced adenomas in the neoplasia analysis owing to insufficient data.
DISCLOSURES:
This study was funded by an investigator grant from the Australia National Health and Medical Research Council and a Cancer Australia/Cancer Council NSW cofunded grant. No relevant conflicts of interest were disclosed by the authors.
This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.
