Prevalence of Genotoxic Bacteria in Men Undergoing Biopsy for Prostate Cancer

Overview

Journal Prostate

Date 2023 Feb 26

PMID 36842100

Authors

John Lee

Brian L Wickes

Jianmin Fu

Nohelli E Brockman

Harshit Garg

Christian Jobin

Teresa Johson-Pais

Robin Leach

Zhao Lai

Michael A Liss

Affiliations

Soon will be listed here.

Abstract

Background: New evidence suggests that bacteria-produced DNA toxins may have a role in the development or progression of prostate cancer. To determine the prevalence of these genes in a noninfection (i.e., colonized) state, we screened urine specimens in men before undergoing a biopsy for prostate cancer detection.

Methods: We developed a multiplex polymerase chain reaction using three of the most described bacterial genotoxin gene primers: Colibactin (polyketone synthase [pks] gene island: clbN and clbB), cytotoxic necrotizing factor (cnf1) toxin, and cytolethal distending toxin B (cdtB) represented gene islands. After calibration on Escherichia coli samples of known genotypes, we used a training and validation cohort. We performed multiplex testing on a training cohort of previously collected urine from 45 men undergoing prostate biopsy. For the validation cohort, we utilized baseline urine samples from a previous randomized clinical trial (n = 263) with known prostate cancer outcomes.

Results: The prevalence of four common bacterial genotoxin genes detected in the urine before prostate biopsy for prostate cancer is 8% (25/311). The prevalence of pks island (clbN and clbB), cnf1, and cdt toxin genes are 6.1%, 2.4%, and 1.7%, respectively. We found no association between urinary genotoxins and prostate cancer (p = 0.83). We did identify a higher proportion of low-grade cancer (92% vs. 44%) in those men positive for urinary genotoxin and higher-grade cancer in those genotoxin negative (8% vs. 56%, p = 0.001).

Conclusions: The prevalence of urinary genotoxins is low and does not correspond to a prostate cancer diagnosis. The urine was taken at one point in time and does not rule out the possibility of previous exposure.

Citing Articles

Prostate cancer microenvironment: multidimensional regulation of immune cells, vascular system, stromal cells, and microbiota.

Chen L, Xu Y, Wang Y, Ren Y, Dong X, Wu P Mol Cancer. 2024; 23(1):229.

PMID: 39395984 PMC: 11470719. DOI: 10.1186/s12943-024-02137-1.

Unveiling the intratumoral microbiota within cancer landscapes.

Che S, Yan Z, Feng Y, Zhao H iScience. 2024; 27(6):109893.

PMID: 38799560 PMC: 11126819. DOI: 10.1016/j.isci.2024.109893.

References

Tomlins S, Aubin S, Siddiqui J, Lonigro R, Sefton-Miller L, Miick S . Urine TMPRSS2:ERG fusion transcript stratifies prostate cancer risk in men with elevated serum PSA. Sci Transl Med. 2011; 3(94):94ra72. PMC: 3245713. DOI: 10.1126/scitranslmed.3001970. View

Cougnoux A, Dalmasso G, Martinez R, Buc E, Delmas J, Gibold L . Bacterial genotoxin colibactin promotes colon tumour growth by inducing a senescence-associated secretory phenotype. Gut. 2014; 63(12):1932-42. DOI: 10.1136/gutjnl-2013-305257. View

Shrestha E, Coulter J, Guzman W, Ozbek B, Hess M, Mummert L . Oncogenic gene fusions in nonneoplastic precursors as evidence that bacterial infection can initiate prostate cancer. Proc Natl Acad Sci U S A. 2021; 118(32). PMC: 8364155. DOI: 10.1073/pnas.2018976118. View

Gao Y, Wei L, Wang C, Huang Y, Li W, Li T . Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice. Biol Res. 2019; 52(1):30. PMC: 6518623. DOI: 10.1186/s40659-019-0237-4. View

Caprioli A, Falbo V, Ruggeri F, Baldassarri L, Bisicchia R, Ippolito G . Cytotoxic necrotizing factor production by hemolytic strains of Escherichia coli causing extraintestinal infections. J Clin Microbiol. 1987; 25(1):146-9. PMC: 265843. DOI: 10.1128/jcm.25.1.146-149.1987. View

Xue M, Kim C, Healy A, Wernke K, Wang Z, Frischling M . Structure elucidation of colibactin and its DNA cross-links. Science. 2019; 365(6457). PMC: 6820679. DOI: 10.1126/science.aax2685. View

Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M . A model for gastric cancer epidemiology. Lancet. 1975; 2(7924):58-60. DOI: 10.1016/s0140-6736(75)90498-5. View

Johnson J, Johnston B, Gordon D . Rapid and Specific Detection of the Escherichia coli Sequence Type 648 Complex within Phylogroup F. J Clin Microbiol. 2017; 55(4):1116-1121. PMC: 5377838. DOI: 10.1128/JCM.01949-16. View

Dejea C, Fathi P, Craig J, Boleij A, Taddese R, Geis A . Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria. Science. 2018; 359(6375):592-597. PMC: 5881113. DOI: 10.1126/science.aah3648. View

10.

Kadhum H, Finlay D, Rowe M, Wilson I, Ball H . Occurrence and characteristics of cytotoxic necrotizing factors, cytolethal distending toxins and other virulence factors in Escherichia coli from human blood and faecal samples. Epidemiol Infect. 2007; 136(6):752-60. PMC: 2870871. DOI: 10.1017/S0950268807009247. View

11.

Puhr M, De Marzo A, Isaacs W, Lucia M, Sfanos K, Yegnasubramanian S . Inflammation, Microbiota, and Prostate Cancer. Eur Urol Focus. 2017; 2(4):374-382. DOI: 10.1016/j.euf.2016.08.010. View

12.

Wilson M, Jiang Y, Villalta P, Stornetta A, Boudreau P, Carra A . The human gut bacterial genotoxin colibactin alkylates DNA. Science. 2019; 363(6428). PMC: 6407708. DOI: 10.1126/science.aar7785. View

13.

Helmink B, Khan M, Hermann A, Gopalakrishnan V, Wargo J . The microbiome, cancer, and cancer therapy. Nat Med. 2019; 25(3):377-388. DOI: 10.1038/s41591-019-0377-7. View

14.

Pleguezuelos-Manzano C, Puschhof J, Rosendahl Huber A, Van Hoeck A, Wood H, Nomburg J . Mutational signature in colorectal cancer caused by genotoxic pks E. coli. Nature. 2020; 580(7802):269-273. PMC: 8142898. DOI: 10.1038/s41586-020-2080-8. View

15.

Li Z, Li J, Cai W, Lai J, McKinnie S, Zhang W . Macrocyclic colibactin induces DNA double-strand breaks via copper-mediated oxidative cleavage. Nat Chem. 2019; 11(10):880-889. PMC: 6761029. DOI: 10.1038/s41557-019-0317-7. View

16.

Toth I, Herault F, Beutin L, Oswald E . Production of cytolethal distending toxins by pathogenic Escherichia coli strains isolated from human and animal sources: establishment of the existence of a new cdt variant (Type IV). J Clin Microbiol. 2003; 41(9):4285-91. PMC: 193864. DOI: 10.1128/JCM.41.9.4285-4291.2003. View

17.

Chapman T, Wu X, Barchia I, Bettelheim K, Driesen S, Trott D . Comparison of virulence gene profiles of Escherichia coli strains isolated from healthy and diarrheic swine. Appl Environ Microbiol. 2006; 72(7):4782-95. PMC: 1489375. DOI: 10.1128/AEM.02885-05. View

18.

Baca S, Prandi D, Lawrence M, Mosquera J, Romanel A, Drier Y . Punctuated evolution of prostate cancer genomes. Cell. 2013; 153(3):666-77. PMC: 3690918. DOI: 10.1016/j.cell.2013.03.021. View

19.

Graillot V, Dormoy I, Dupuy J, Shay J, Huc L, Mirey G . Genotoxicity of Cytolethal Distending Toxin (CDT) on Isogenic Human Colorectal Cell Lines: Potential Promoting Effects for Colorectal Carcinogenesis. Front Cell Infect Microbiol. 2016; 6:34. PMC: 4803749. DOI: 10.3389/fcimb.2016.00034. View

20.

Guidi R, Guerra L, Levi L, Stenerlow B, Fox J, Josenhans C . Chronic exposure to the cytolethal distending toxins of Gram-negative bacteria promotes genomic instability and altered DNA damage response. Cell Microbiol. 2012; 15(1):98-113. PMC: 4136655. DOI: 10.1111/cmi.12034. View