Abstract
Introduction: According to GLOBOCAN estimates, colorectal cancer (CRC) was the third most common cancer worldwide in 2020, comprising 11% of all cancer diagnoses. Researchers’ interest in CRC development has shifted toward the gastrointestinal microbiome, especially the mutagenicity of pks+ E. coli. Therefore, we aimed to review the current evidence on the relationship between pks+ E. coli and CRC.
Method: We reviewed the literature reporting the association between pks+ E. coli and CRC, which was obtained from three databases: PubMed, Google Scholar, and the Cochrane Library, published between January 2021 and January 2026. We used the following keywords for our search strategy: pks, Escherichia coli, and colorectal cancer.
Result: As stated in the original studies, the contribution of pks+ E. coli to CRC development was associated with a higher prevalence in the CRC group than in the healthy group. However, these results are inconsistent across the studies.
Conclusion: Given the limited evidence, researchers should conduct larger cohort studies to clarify this relationship and identify other factors contributing to the presence of pks+ E. coli, particularly across diverse clinical settings. Furthermore, clinical translation, such as the utilization of screening or therapeutic biomarkers, requires prospective validation and standardized detection methods.
References
1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018: 394 [PMID: 30207593, https://doi.org/10.3322/caac.21492]
2. Globocan. Global Cancer Observatory: Cancer Today:
3. Fu M, Li Y, Wang J. Incidence and Mortality of Colorectal Cancer in Asia in 2022 and Projections for 2050. J Gastroenterol Hepatol. 2025: 1143 [PMID: 40018878, https://doi.org/10.1111/jgh.16910]
4. Tsedendorj Y, Zorigtbaatar S, Davaasuren NE, Dondov G, Ganbat T, Lonjid T, Batsaikhan A, Tudev U, Batsaikhan B. Incidence and Mortality due to Colorectal Cancer in Mongolia, 2018-2022. Asian Pac J Cancer Prev. 2024: 2305 [PMID: 39068562, https://doi.org/10.31557/APJCP.2024.25.7.2305]
5. Lichtenstein P, Holm NV, Verkasalo PK, Iliadou A, Kaprio J, Koskenvuo M, Pukkala E, Skytthe A, Hemminki K. Environmental and heritable factors in the causation of cancer--analyses of cohorts of twins from Sweden, Denmark, and Finland. N Engl J Med. 2000: 78 [PMID: 10891514, https://doi.org/10.1056/NEJM200007133430201]
6. Mucci LA, Hjelmborg JB, Harris JR, Czene K, Havelick DJ, Scheike T, Graff RE, Holst K, Moller S, Unger RH, McIntosh C, Nuttall E, Brandt I, Penney KL, Hartman M, Kraft P, Parmigiani G, Christensen K, Koskenvuo M, Holm NV, Heikkila K, Pukkala E, Skytthe A, Adami HO, Kaprio J, Nordic Twin Study of Cancer C. Familial Risk and Heritability of Cancer Among Twins in Nordic Countries. JAMA. 2016: 68 [PMID: 26746459, https://doi.org/10.1001/jama.2015.17703]
7. McNabb S, Harrison TA, Albanes D, Berndt SI, Brenner H, Caan BJ, Campbell PT, Cao Y, Chang-Claude J, Chan A, Chen Z, English DR, Giles GG, Giovannucci EL, Goodman PJ, Hayes RB, Hoffmeister M, Jacobs EJ, Joshi AD, Larsson SC, Le Marchand L, Li L, Lin Y, Mannisto S, Milne RL, Nan H, Newton CC, Ogino S, Parfrey PS, Petersen PS, Potter JD, Schoen RE, Slattery ML, Su YR, Tangen CM, Tucker TC, Weinstein SJ, White E, Wolk A, Woods MO, Phipps AI, Peters U. Meta-analysis of 16 studies of the association of alcohol with colorectal cancer. Int J Cancer. 2020: 861 [PMID: 31037736, https://doi.org/10.1002/ijc.32377]
8. Botteri E, Borroni E, Sloan EK, Bagnardi V, Bosetti C, Peveri G, Santucci C, Specchia C, van den Brandt P, Gallus S, Lugo A. Smoking and Colorectal Cancer Risk, Overall and by Molecular Subtypes: A Meta-Analysis. Am J Gastroenterol. 2020: 1940 [PMID: 32773458, https://doi.org/10.14309/ajg.0000000000000803]
9. Socol CT, Chira A, Martinez-Sanchez MA, Nunez-Sanchez MA, Maerescu CM, Mierlita D, Rusu AV, Ruiz-Alcaraz AJ, Trif M, Ramos-Molina B. Leptin Signaling in Obesity and Colorectal Cancer. Int J Mol Sci. 2022: [PMID: 35563103, https://doi.org/10.3390/ijms23094713]
10. Veettil SK, Wong TY, Loo YS, Playdon MC, Lai NM, Giovannucci EL, Chaiyakunapruk N. Role of Diet in Colorectal Cancer Incidence: Umbrella Review of Meta-analyses of Prospective Observational Studies. JAMA Netw Open. 2021: e2037341 [PMID: 33591366, https://doi.org/10.1001/jamanetworkopen.2020.37341]
11. Morrison DS, Parr CL, Lam TH, Ueshima H, Kim HC, Jee SH, Murakami Y, Giles G, Fang X, Barzi F, Batty GD, Huxley RR, Woodward M. Behavioural and metabolic risk factors for mortality from colon and rectum cancer: analysis of data from the Asia-Pacific Cohort Studies Collaboration. Asian Pac J Cancer Prev. 2013: 1083 [PMID: 23621191, https://doi.org/10.7314/apjcp.2013.14.2.1083]
12. Kikuchi N, Nishiyama T, Sawada T, Wang C, Lin Y, Watanabe Y, Tamakoshi A, Kikuchi S. Perceived Stress and Colorectal Cancer Incidence: The Japan Collaborative Cohort Study. Sci Rep. 2017: 40363 [PMID: 28091607, https://doi.org/10.1038/srep40363]
13. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, Bray F. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA Cancer J Clin. 2021: 209 [PMID: 33538338, https://doi.org/10.3322/caac.21660]
14. Pearlman R, Frankel WL, Swanson B, Zhao W, Yilmaz A, Miller K, Bacher J, Bigley C, Nelsen L, Goodfellow PJ, Goldberg RM, Paskett E, Shields PG, Freudenheim JL, Stanich PP, Lattimer I, Arnold M, Liyanarachchi S, Kalady M, Heald B, Greenwood C, Paquette I, Prues M, Draper DJ, Lindeman C, Kuebler JP, Reynolds K, Brell JM, Shaper AA, Mahesh S, Buie N, Weeman K, Shine K, Haut M, Edwards J, Bastola S, Wickham K, Khanduja KS, Zacks R, Pritchard CC, Shirts BH, Jacobson A, Allen B, de la Chapelle A, Hampel H, Ohio Colorectal Cancer Prevention Initiative Study G. Prevalence and Spectrum of Germline Cancer Susceptibility Gene Mutations Among Patients With Early-Onset Colorectal Cancer. JAMA Oncol. 2017: 464 [PMID: 27978560, https://doi.org/10.1001/jamaoncol.2016.5194]
15. Ho CH, Cheng KC, Chao CM, Lai CC, Chiang SR, Chen CM, Liao KM, Wang JJ, Lee PH, Hung CM, Tai CM, Chiu CC. Does radiotherapy increase the risk of colorectal cancer among prostate cancer patients? A large population-based study. J Cancer. 2020: 6204 [PMID: 33033503, https://doi.org/10.7150/jca.44726]
16. Taylor DP, Burt RW, Williams MS, Haug PJ, Cannon-Albright LA. Population-based family history-specific risks for colorectal cancer: a constellation approach. Gastroenterology. 2010: 877 [PMID: 19932107, https://doi.org/10.1053/j.gastro.2009.11.044]
17. Roshandel G, Ghasemi-Kebria F, Malekzadeh R. Colorectal Cancer: Epidemiology, Risk Factors, and Prevention. Cancers (Basel). 2024: [PMID: 38672612, https://doi.org/10.3390/cancers16081530]
18. Badero OJ, Meribole ES, Omokore O, Quadri IO, Kingdom P, Ifeanyichukwu OC, Ogunnoiki SO, Samuel-Ogunnoiki PM, Adeyoola O, Osibowale B, Chima-Ogbuiyi N, Buari MO, Umeh J, Adeyemi A. Gut Microbiota and Colorectal Cancer: Is Microbial Dysbiosis in Carcinogenesis an Emerging Risk Factor? Cureus. 2026: e102283 [PMID: 41602516, https://doi.org/10.7759/cureus.102283]
19. Gacesa R, Kurilshikov A, Vich Vila A, Sinha T, Klaassen MAY, Bolte LA, Andreu-Sanchez S, Chen L, Collij V, Hu S, Dekens JAM, Lenters VC, Bjork JR, Swarte JC, Swertz MA, Jansen BH, Gelderloos-Arends J, Jankipersadsing S, Hofker M, Vermeulen RCH, Sanna S, Harmsen HJM, Wijmenga C, Fu J, Zhernakova A, Weersma RK. Environmental factors shaping the gut microbiome in a Dutch population. Nature. 2022: 732 [PMID: 35418674, https://doi.org/10.1038/s41586-022-04567-7]
20. Gomaa EZ. Human gut microbiota/microbiome in health and diseases: a review. Antonie Van Leeuwenhoek. 2020: 2019 [PMID: 33136284, https://doi.org/10.1007/s10482-020-01474-7]
21. Sobhani I, Amiot A, Le Baleur Y, Levy M, Auriault ML, Van Nhieu JT, Delchier JC. Microbial dysbiosis and colon carcinogenesis: could colon cancer be considered a bacteria-related disease? Therap Adv Gastroenterol. 2013: 215 [PMID: 23634186, https://doi.org/10.1177/1756283X12473674]
22. Tlaskalova-Hogenova H, Stepankova R, Hudcovic T, Tuckova L, Cukrowska B, Lodinova-Zadnikova R, Kozakova H, Rossmann P, Bartova J, Sokol D, Funda DP, Borovska D, Rehakova Z, Sinkora J, Hofman J, Drastich P, Kokesova A. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett. 2004: 97 [PMID: 15158604, https://doi.org/10.1016/j.imlet.2004.02.005]
23. Gaab ME, Lozano PO, Ibanez D, Manese KD, Riego FM, Tiongco RE, Albano PM. A Meta-Analysis on the Association of Colibactin-Producing pks+ Escherichia coli with the Development of Colorectal Cancer. Lab Med. 2023: 75 [PMID: 35960765, https://doi.org/10.1093/labmed/lmac072]
24. Hall AB, Tolonen AC, Xavier RJ. Human genetic variation and the gut microbiome in disease. Nat Rev Genet. 2017: 690 [PMID: 28824167, https://doi.org/10.1038/nrg.2017.63]
25. Gomes TA, Elias WP, Scaletsky IC, Guth BE, Rodrigues JF, Piazza RM, Ferreira LC, Martinez MB. Diarrheagenic Escherichia coli. Braz J Microbiol. 2016: 3 [PMID: 27866935, https://doi.org/10.1016/j.bjm.2016.10.015]
26. Palaniappan RU, Zhang Y, Chiu D, Torres A, Debroy C, Whittam TS, Chang YF. Differentiation of Escherichia coli pathotypes by oligonucleotide spotted array. J Clin Microbiol. 2006: 1495 [PMID: 16597882, https://doi.org/10.1128/JCM.44.4.1495-1501.2006]
27. Mitsuoka T, Hayakawa K. [The fecal flora in man. I. Composition of the fecal flora of various age groups]:
28. Penders J, Thijs C, Vink C, Stelma FF, Snijders B, Kummeling I, van den Brandt PA, Stobberingh EE. Factors influencing the composition of the intestinal microbiota in early infancy. Pediatrics. 2006: 511 [PMID: 16882802, https://doi.org/10.1542/peds.2005-2824]
29. Gordon DM, Cowling A. The distribution and genetic structure of Escherichia coli in Australian vertebrates: host and geographic effects. Microbiology (Reading). 2003: 3575 [PMID: 14663089, https://doi.org/10.1099/mic.0.26486-0]
30. Ochoa TJ, Barletta F, Contreras C, Mercado E. New insights into the epidemiology of enteropathogenic Escherichia coli infection. Trans R Soc Trop Med Hyg. 2008: 852 [PMID: 18455741, https://doi.org/10.1016/j.trstmh.2008.03.017]
31. Kralicek SE, Sitaraman LM, Kuprys PV, Harrington AT, Ramakrishna B, Osman M, Hecht GA. Clinical Manifestations and Stool Load of Atypical Enteropathogenic Escherichia coli Infections in United States Children and Adults. Gastroenterology. 2022: 1321 [PMID: 35948108, https://doi.org/10.1053/j.gastro.2022.07.064]
32. Majowicz SE, Scallan E, Jones-Bitton A, Sargeant JM, Stapleton J, Angulo FJ, Yeung DH, Kirk MD. Global incidence of human Shiga toxin-producing Escherichia coli infections and deaths: a systematic review and knowledge synthesis. Foodborne Pathog Dis. 2014: 447 [PMID: 24750096, https://doi.org/10.1089/fpd.2013.1704]
33. Vieira N, Bates SJ, Solberg OD, Ponce K, Howsmon R, Cevallos W, Trueba G, Riley LEE, Eisenberg JNS. High Prevalence of Enteroinvasive Escherichia Coli Isolated in a Remote Region of Northern Coastal Ecuador. The American Journal of Tropical Medicine and Hygiene. 2007: 528 https://doi.org/10.4269/ajtmh.2007.76.528]
34. van den Beld MJ, Reubsaet FA. Differentiation between Shigella, enteroinvasive Escherichia coli (EIEC) and noninvasive Escherichia coli. Eur J Clin Microbiol Infect Dis. 2012: 899 [PMID: 21901636, https://doi.org/10.1007/s10096-011-1395-7]
35. Khalil IA, Troeger C, Blacker BF, Rao PC, Brown A, Atherly DE, Brewer TG, Engmann CM, Houpt ER, Kang G, Kotloff KL, Levine MM, Luby SP, MacLennan CA, Pan WK, Pavlinac PB, Platts-Mills JA, Qadri F, Riddle MS, Ryan ET, Shoultz DA, Steele AD, Walson JL, Sanders JW, Mokdad AH, Murray CJL, Hay SI, Reiner RC, Jr. Morbidity and mortality due to shigella and enterotoxigenic Escherichia coli diarrhoea: the Global Burden of Disease Study 1990-2016. Lancet Infect Dis. 2018: 1229 [PMID: 30266330, https://doi.org/10.1016/S1473-3099(18)30475-4]
36. Shah N, DuPont HL, Ramsey DJ. Global Etiology of Travelers’ Diarrhea: Systematic Review from 1973 to the Present. The American Journal of Tropical Medicine and Hygiene. 2009: 609 https://doi.org/10.4269/ajtmh.2009.80.609]
37. Khuntia HK, Manna P, Barik DK, Biswas S, Bramha PK, Pati S, Ranjit M, Bal M, Kerketta AS. High prevalence of enterotoxigenic Escherichia coli strains in hospitalized diarrhea patients: a preliminary study from a cholera-endemic area in India (2022). Front Microbiol. 2025: 1470783 [PMID: 40535018, https://doi.org/10.3389/fmicb.2025.1470783]
38. Chowdhury F, Islam MT, Ahmmed F, Akter A, Mwebia MB, Im J, Rickett NY, Mbae CK, Aziz AB, Ongadi B, Khanam F, Khan AI, Firoj MG, Rahman SIA, Park SE, Haile K, Mwangi M, Ngugi B, Behute MG, Kering K, Agampodi S, Kanungo S, Zaman K, Kariuki S, Qadri F, Clemens JD. Epidemiological and Clinical Features of Enterotoxigenic Escherichia coli (ETEC) Diarrhea in an Urban Slum in Dhaka, Bangladesh. Open Forum Infect Dis. 2025: ofaf375 [PMID: 40689249, https://doi.org/10.1093/ofid/ofaf375]
39. Wanke CA, Schorling JB, Barrett LJ, Desouza MA, Guerrant RL. Potential role of adherence traits of Escherichia coli in persistent diarrhea in an urban Brazilian slum. Pediatr Infect Dis J. 1991: 746 [PMID: 1658721, https://doi.org/10.1097/00006454-199110000-00006]
40. Mathewson JJ, Jiang ZD, Zumla A, Chintu C, Luo N, Calamari SR, Genta RM, Steephen A, Schwartz P, DuPont HL. HEp-2 cell-adherent Escherichia coli in patients with human immunodeficiency virus-associated diarrhea. J Infect Dis. 1995: 1636 [PMID: 7769307, https://doi.org/10.1093/infdis/171.6.1636]
41. Peng Z, Wang X, Huang J, Li B. Pathogenic Escherichia coli. Molecular Medical Microbiology2024. p. 1065-1096.
42. Spano LC, Sadovsky ADI, Segui PN, Saick KW, Kitagawa SMS, Pereira FEL, Fagundes-Neto U, Scaletsky ICA. Age-specific prevalence of diffusely adherent Escherichia coli in Brazilian children with acute diarrhoea. J Med Microbiol. 2008: 359 [PMID: 18287300, https://doi.org/10.1099/jmm.0.47660-0]
43. Abbasi P, Kargar M, Doosti A, Mardaneh J, Ghorbani-Dalini S, Dehyadegari MA. Molecular Detection of Diffusely Adherent Escherichia coli Strains Associated with Diarrhea in Shiraz, Iran. Archives of Pediatric Infectious Diseases. 2016: https://doi.org/10.5812/pedinfect.37629]
44. Baqui AH, Sack RB, Black RE, Haider K, Hossain A, Alim AR, Yunus M, Chowdhury HR, Siddique AK. Enteropathogens associated with acute and persistent diarrhea in Bangladeshi children less than 5 years of age. J Infect Dis. 1992: 792 [PMID: 1527413, https://doi.org/10.1093/infdis/166.4.792]
45. Medina M, Castillo-Pino E. An introduction to the epidemiology and burden of urinary tract infections. Ther Adv Urol. 2019: 1756287219832172 [PMID: 31105774, https://doi.org/10.1177/1756287219832172]
46. Terlizzi ME, Gribaudo G, Maffei ME. UroPathogenic Escherichia coli (UPEC) Infections: Virulence Factors, Bladder Responses, Antibiotic, and Non-antibiotic Antimicrobial Strategies. Front Microbiol. 2017: 1566 [PMID: 28861072, https://doi.org/10.3389/fmicb.2017.01566]
47. Glik J, Kawecki M, Gazdzik T, Nowak M. The impact of the types of microorganisms isolated from blood and wounds on the results of treatment in burn patients with sepsis. Pol Przegl Chir. 2012: 6 [PMID: 22472489, https://doi.org/10.2478/v10035-012-0002-7]
48. Lee P, Sin E, Yip KT, Ng K. A 10-Year Study of Neonatal Sepsis from Tuen Mun Hospital, Hong Kong. Pathogens. 2025: [PMID: 40137761, https://doi.org/10.3390/pathogens14030276]
49. Wijetunge DS, Gongati S, DebRoy C, Kim KS, Couraud PO, Romero IA, Weksler B, Kariyawasam S. Characterizing the pathotype of neonatal meningitis causing Escherichia coli (NMEC). BMC Microbiol. 2015: 211 [PMID: 26467858, https://doi.org/10.1186/s12866-015-0547-9]
50. Kamali Dolatabadi R, Feizi A, Halaji M, Fazeli H, Adibi P. The Prevalence of Adherent-Invasive Escherichia coli and Its Association With Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis. Front Med (Lausanne). 2021: 730243 [PMID: 34926490, https://doi.org/10.3389/fmed.2021.730243]
51. Kostic AD, Xavier RJ, Gevers D. The microbiome in inflammatory bowel disease: current status and the future ahead. Gastroenterology. 2014: 1489 [PMID: 24560869, https://doi.org/10.1053/j.gastro.2014.02.009]
52. Iyadorai T, Mariappan V, Vellasamy KM, Wanyiri JW, Roslani AC, Lee GK, Sears C, Vadivelu J. Prevalence and association of pks+ Escherichia coli with colorectal cancer in patients at the University Malaya Medical Centre, Malaysia. PLoS One. 2020: e0228217 [PMID: 31990962, https://doi.org/10.1371/journal.pone.0228217]
53. de Klaver W, de Wit M, Bolijn A, Tijssen M, Delis-van Diemen P, Lemmens M, Spaander MC, Dekker E, van Leerdam ME, Coupe VM, van Boxtel R, Clevers H, Carvalho B, Meijer GA. Polyketide synthase positive Escherichia coli one-time measurement in stool is not informative of colorectal cancer risk in a screening setting. J Pathol. 2024: 217 [PMID: 38551073, https://doi.org/10.1002/path.6276]
54. Liu K, Yang X, Zeng M, Yuan Y, Sun J, He P, Sun J, Xie Q, Chang X, Zhang S, Chen X, Cai L, Xie Y, Jiao X. The Role of Fecal Fusobacterium nucleatum and pks(+) Escherichia coli as Early Diagnostic Markers of Colorectal Cancer. Dis Markers. 2021: 1171239 [PMID: 34853619, https://doi.org/10.1155/2021/1171239]
55. Oliero M, Hajjar R, Cuisiniere T, Fragoso G, Calve A, Dagbert F, Loungnarath R, Sebajang H, Schwenter F, Wassef R, Ratelle R, De Broux E, Richard CS, Santos MM. Prevalence of pks + bacteria and enterotoxigenic Bacteroides fragilis in patients with colorectal cancer. Gut Pathog. 2022: 51 [PMID: 36578036, https://doi.org/10.1186/s13099-022-00523-y]
56. Joo JE, Chu YL, Georgeson P, Walker R, Mahmood K, Clendenning M, Meyers AL, Como J, Joseland S, Preston SG, Diepenhorst N, Toner J, Ingle DJ, Sherry NL, Metz A, Lynch BM, Milne RL, Southey MC, Hopper JL, Win AK, Macrae FA, Winship IM, Rosty C, Jenkins MA, Buchanan DD. 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. Br J Cancer. 2024: 728 [PMID: 38200234, https://doi.org/10.1038/s41416-023-02554-x]
57. Miyasaka T, Yamada T, Uehara K, Sonoda H, Matsuda A, Shinji S, Ohta R, Kuriyama S, Yokoyama Y, Takahashi G, Iwai T, Takeda K, Ueda K, Kanaka S, Ohashi R, Yoshida H. Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients. Cancer Sci. 2024: 1184 [PMID: 38297479, https://doi.org/10.1111/cas.16088]
58. Chen B, Ramazzotti D, Heide T, Spiteri I, Fernandez-Mateos J, James C, Magnani L, Graham TA, Sottoriva A. Contribution of pks(+) E. coli mutations to colorectal carcinogenesis. Nat Commun. 2023: 7827 [PMID: 38030613, https://doi.org/10.1038/s41467-023-43329-5]
59. Chu YL, Georgeson P, Clendenning M, Mahmood K, Walker R, Como J, Joseland S, Preston SG, Rice T, Lynch BM, Milne RL, Southey MC, Giles GG, Phipps AI, Hopper JL, Win AK, Rosty C, Macrae FA, Winship I, Jenkins MA, Buchanan DD, Joo JE. Intratumoural pks(+)Escherichia coli is associated with risk of metachronous colorectal cancer and adenoma development in people with Lynch syndrome. EBioMedicine. 2025: 105661 [PMID: 40158390, https://doi.org/10.1016/j.ebiom.2025.105661]
60. Groisman EA, Ochman H. Pathogenicity islands: bacterial evolution in quantum leaps. Cell. 1996: 791 [PMID: 8945505, https://doi.org/10.1016/s0092-8674(00)81985-6]
61. Putze J, Hennequin C, Nougayrede JP, Zhang W, Homburg S, Karch H, Bringer MA, Fayolle C, Carniel E, Rabsch W, Oelschlaeger TA, Oswald E, Forestier C, Hacker J, Dobrindt U. Genetic structure and distribution of the colibactin genomic island among members of the family Enterobacteriaceae. Infect Immun. 2009: 4696 [PMID: 19720753, https://doi.org/10.1128/IAI.00522-09]
62. Addington E, Sandalli S, Roe AJ. Current understandings of colibactin regulation. Microbiology (Reading). 2024: [PMID: 38314762, https://doi.org/10.1099/mic.0.001427]
63. Sadeghi M, Mestivier D, Sobhani I. Contribution of pks+ Escherichia coli (E. coli) to Colon Carcinogenesis. Microorganisms. 2024: [PMID: 38930493, https://doi.org/10.3390/microorganisms12061111]
64. Nougayrede JP, Homburg S, Taieb F, Boury M, Brzuszkiewicz E, Gottschalk G, Buchrieser C, Hacker J, Dobrindt U, Oswald E. Escherichia coli induces DNA double-strand breaks in eukaryotic cells. Science. 2006: 848 [PMID: 16902142, https://doi.org/10.1126/science.1127059]
65. Mousa JJ, Yang Y, Tomkovich S, Shima A, Newsome RC, Tripathi P, Oswald E, Bruner SD, Jobin C. MATE transport of the E. coli-derived genotoxin colibactin. Nat Microbiol. 2016: 15009 [PMID: 27571755, https://doi.org/10.1038/nmicrobiol.2015.9]
66. Bian X, Plaza A, Zhang Y, Muller R. Two more pieces of the colibactin genotoxin puzzle from Escherichia coli show incorporation of an unusual 1-aminocyclopropanecarboxylic acid moiety. Chem Sci. 2015: 3154 [PMID: 28706687, https://doi.org/10.1039/c5sc00101c]
67. Tang-Fichaux M, Chagneau CV, Bossuet-Greif N, Nougayrede JP, Oswald E, Branchu P. The Polyphosphate Kinase of Escherichia coli Is Required for Full Production of the Genotoxin Colibactin. mSphere. 2020: [PMID: 33328353, https://doi.org/10.1128/mSphere.01195-20]
68. Pino MS, Chung DC. The chromosomal instability pathway in colon cancer. Gastroenterology. 2010: 2059 [PMID: 20420946, https://doi.org/10.1053/j.gastro.2009.12.065]
69. Martincorena I, Raine KM, Gerstung M, Dawson KJ, Haase K, Van Loo P, Davies H, Stratton MR, Campbell PJ. Universal Patterns of Selection in Cancer and Somatic Tissues. Cell. 2017: 1029 [PMID: 29056346, https://doi.org/10.1016/j.cell.2017.09.042]
70. Vogelstein B, Papadopoulos N, Velculescu VE, Zhou S, Diaz LA, Jr., Kinzler KW. Cancer genome landscapes. Science. 2013: 1546 [PMID: 23539594, https://doi.org/10.1126/science.1235122]
71. Lee-Six H, Olafsson S, Ellis P, Osborne RJ, Sanders MA, Moore L, Georgakopoulos N, Torrente F, Noorani A, Goddard M, Robinson P, Coorens THH, O'Neill L, Alder C, Wang J, Fitzgerald RC, Zilbauer M, Coleman N, Saeb-Parsy K, Martincorena I, Campbell PJ, Stratton MR. The landscape of somatic mutation in normal colorectal epithelial cells. Nature. 2019: 532 [PMID: 31645730, https://doi.org/10.1038/s41586-019-1672-7]
72. Wirbel J, Pyl PT, Kartal E, Zych K, Kashani A, Milanese A, Fleck JS, Voigt AY, Palleja A, Ponnudurai R, Sunagawa S, Coelho LP, Schrotz-King P, Vogtmann E, Habermann N, Nimeus E, Thomas AM, Manghi P, Gandini S, Serrano D, Mizutani S, Shiroma H, Shiba S, Shibata T, Yachida S, Yamada T, Waldron L, Naccarati A, Segata N, Sinha R, Ulrich CM, Brenner H, Arumugam M, Bork P, Zeller G. Meta-analysis of fecal metagenomes reveals global microbial signatures that are specific for colorectal cancer. Nat Med. 2019: 679 [PMID: 30936547, https://doi.org/10.1038/s41591-019-0406-6]
73. Xue M, Kim CS, Healy AR, Wernke KM, Wang Z, Frischling MC, Shine EE, Wang W, Herzon SB, Crawford JM. Structure elucidation of colibactin and its DNA cross-links. Science. 2019: [PMID: 31395743, https://doi.org/10.1126/science.aax2685]
74. Cuevas-Ramos G, Petit CR, Marcq I, Boury M, Oswald E, Nougayrede JP. Escherichia coli induces DNA damage in vivo and triggers genomic instability in mammalian cells. Proc Natl Acad Sci U S A. 2010: 11537 [PMID: 20534522, https://doi.org/10.1073/pnas.1001261107]
75. Pleguezuelos-Manzano C, Puschhof J, Rosendahl Huber A, van Hoeck A, Wood HM, Nomburg J, Gurjao C, Manders F, Dalmasso G, Stege PB, Paganelli FL, Geurts MH, Beumer J, Mizutani T, Miao Y, van der Linden R, van der Elst S, Genomics England Research C, Garcia KC, Top J, Willems RJL, Giannakis M, Bonnet R, Quirke P, Meyerson M, Cuppen E, van Boxtel R, Clevers H. Mutational signature in colorectal cancer caused by genotoxic pks(+) E. coli. Nature. 2020: 269 [PMID: 32106218, https://doi.org/10.1038/s41586-020-2080-8]
76. Rosendahl Huber A, Pleguezuelos-Manzano C, Puschhof J, Ubels J, Boot C, Saftien A, Verheul M, Trabut LT, Groenen N, van Roosmalen M, Ouyang KS, Wood H, Quirke P, Meijer G, Cuppen E, Clevers H, van Boxtel R. Improved detection of colibactin-induced mutations by genotoxic E. coli in organoids and colorectal cancer. Cancer Cell. 2024: 487 [PMID: 38471458, https://doi.org/10.1016/j.ccell.2024.02.009]
77. Dougherty MW, Jobin C. Shining a Light on Colibactin Biology. Toxins (Basel). 2021: [PMID: 34065799, https://doi.org/10.3390/toxins13050346]
78. Dejea CM, Fathi P, Craig JM, Boleij A, Taddese R, Geis AL, Wu X, DeStefano Shields CE, Hechenbleikner EM, Huso DL, Anders RA, Giardiello FM, Wick EC, Wang H, Wu S, Pardoll DM, Housseau F, Sears CL. Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018: 592 [PMID: 29420293, https://doi.org/10.1126/science.aah3648]
79. Eklof V, Lofgren-Burstrom A, Zingmark C, Edin S, Larsson P, Karling P, Alexeyev O, Rutegard J, Wikberg ML, Palmqvist R. Cancer-associated fecal microbial markers in colorectal cancer detection. Int J Cancer. 2017: 2528 [PMID: 28833079, https://doi.org/10.1002/ijc.31011]
80. Iwasaki M, Kanehara R, Yamaji T, Katagiri R, Mutoh M, Tsunematsu Y, Sato M, Watanabe K, Hosomi K, Kakugawa Y, Ikematsu H, Hotta K, Kunisawa J, Wakabayashi K, Matsuda T. Association of Escherichia coli containing polyketide synthase in the gut microbiota with colorectal neoplasia in Japan. Cancer Sci. 2022: 277 [PMID: 34779109, https://doi.org/10.1111/cas.15196]
81. Keum N, Giovannucci E. Global burden of colorectal cancer: emerging trends, risk factors and prevention strategies. Nat Rev Gastroenterol Hepatol. 2019: 713 [PMID: 31455888, https://doi.org/10.1038/s41575-019-0189-8]
82. Song M, Garrett WS, Chan AT. Nutrients, foods, and colorectal cancer prevention. Gastroenterology. 2015: 1244 [PMID: 25575572, https://doi.org/10.1053/j.gastro.2014.12.035]
83. Diaz-Gay M, Dos Santos W, Moody S, Kazachkova M, Abbasi A, Steele CD, Vangara R, Senkin S, Wang J, Fitzgerald S, Bergstrom EN, Khandekar A, Otlu B, Abedi-Ardekani B, de Carvalho AC, Cattiaux T, Penha RCC, Gaborieau V, Chopard P, Carreira C, Cheema S, Latimer C, Teague JW, Mukeriya A, Zaridze D, Cox R, Albert M, Phouthavongsy L, Gallinger S, Malekzadeh R, Niavarani A, Miladinov M, Eric K, Milosavljevic S, Sangrajrang S, Curado MP, Aguiar S, Reis RM, Reis MT, Romagnolo LG, Guimaraes DP, Holcatova I, Kalvach J, Vaccaro CA, Pinero TA, Swiatkowska B, Lissowska J, Roszkowska-Purska K, Huertas-Salgado A, Shibata T, Shiba S, Sangkhathat S, Chitapanarux T, Roshandel G, Ashton-Prolla P, Damin DC, de Oliveira FH, Humphreys L, Lawley TD, Perdomo S, Stratton MR, Brennan P, Alexandrov LB. Geographic and age variations in mutational processes in colorectal cancer. Nature. 2025: 230 [PMID: 40267983, https://doi.org/10.1038/s41586-025-09025-8]
84. Arrieta MC, Stiemsma LT, Amenyogbe N, Brown EM, Finlay B. The intestinal microbiome in early life: health and disease. Front Immunol. 2014: 427 [PMID: 25250028, https://doi.org/10.3389/fimmu.2014.00427]
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