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. 2025 Apr:114:105661.
doi: 10.1016/j.ebiom.2025.105661. Epub 2025 Mar 29.

Intratumoural pks+Escherichia coli is associated with risk of metachronous colorectal cancer and adenoma development in people with Lynch syndrome

Yen Lin Chu  1 , Peter Georgeson  1 , Mark Clendenning  1 , Khalid Mahmood  2 , Romy Walker  1 , Julia Como  1 , Sharelle Joseland  1 , Susan G Preston  1 , Toni Rice  1 , Brigid M Lynch  3 , Roger L Milne  4 , Melissa C Southey  5 , Graham G Giles  4 , Amanda I Phipps  6 , John L Hopper  7 , Aung K Win  7 , Christophe Rosty  8 , Finlay A Macrae  9 , Ingrid Winship  10 , Mark A Jenkins  7 , Daniel D Buchanan  11 , Jihoon E Joo  12
Affiliations

Intratumoural pks+Escherichia coli is associated with risk of metachronous colorectal cancer and adenoma development in people with Lynch syndrome

Yen Lin Chu et al. EBioMedicine. 2025 Apr.

Abstract

Background: The adverse gut microbiome may underlie the variability in risks of colorectal cancer (CRC) and metachronous CRC in people with Lynch syndrome (LS). The role of pks+/-Escherichia coli (pks+/-E. coli), Enterotoxigenic Bacteroides fragilis (ETBF), and Fusobacterium nucleatum (Fn) in CRCs and adenomas in people with LS is unknown.

Methods: A total of 358 LS cases, including 386 CRCs, 90 adenomas, 195 normal colonic mucosa DNA from the Australasian Colon Cancer Family Registry were tested using multiplex TaqMan qPCR. Logistic regression was used to compare the intratumoural prevalence of each bacteria in Lynch CRCs with 1336 sporadic CRCs. Cox proportional-hazards regression estimated the associations of each bacteria with the risk of metachronous CRC and neoplasia.

Findings: Pks+ E. coli (odds ratio [95% confidence interval] = 1.60 [1.08-2.35], P = 0.017), pks-E. coli (3.87 [2.58-5.80], P < 0.001) and Fn (19.47 [13.32-28.87], P < 0.001) were significantly enriched in LS CRCs when compared with sporadic CRCs. Pks+ E. coli in the initial CRC was associated with an increased risk of metachronous CRC (hazard ratio [95% confidence interval] = 2.32 [1.29-4.17], P = 0.005) and metachronous colorectal neoplasia (1.51 [1.02-2.23], P = 0.040) when compared with CRCs without pks+ E. coli.

Interpretation: Pks+ E. coli, pks-E. coli, and Fn are enriched within LS CRCs, suggesting possible roles in CRC development in LS. Having intratumoural pks+ E. coli is associated with increased risk of metachronous CRC, suggesting that, if validated, people with LS might benefit from pks+ E. coli screening and eradication.

Funding: This work was funded by an NHMRC Investigator grant (GNT1194896) and a Cancer Australia/Cancer Council NSW co-funded grant (GNT2012914).

Keywords: Enterotoxigenic Bacteroides fragilis; Fusobacterium nucleatum; Lynch syndrome; Metachronous CRCs; pks(+)E. coli.

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Conflict of interest statement

Declaration of interests The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
The Kaplan–Meier plots showing the association between the presence of (a) pks+E. coli, (b) pks−E. coli, (c) Fusobacterium nucleatum (Fn), and (d) Enterotoxigenic Bacteroides fragilis (ETBF) with the cumulative risk of metachronous CRCs development. The association between pks+E. coli and metachronous cancer risk stratified by (e) MLH1 and (f) MSH2 genes is shown. The test was not adjusted.
Fig. 2
Fig. 2
The Kaplan–Meier plot showing the association between the presence of (a) pks+E. coli, (b) pks−E. coli, (c) Fusobacterium nucleatum (Fn), and (d) Enterotoxigenic Bacteroides fragilis (ETBF) with the cumulative risk of metachronous lesions development. We also showed the association between pks+E. coli and metachronous neoplasms risk stratified by (e) MLH1 and (f) MSH2 genes. The test was not adjusted.
See this image and copyright information in PMC

References

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