Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2023 May;83(7):663-669.
doi: 10.1002/pros.24500. Epub 2023 Feb 26.

Prevalence of genotoxic bacteria in men undergoing biopsy for prostate cancer

John Lee  1 , Brian L Wickes  2 , Jianmin Fu  2 , Nohelli E Brockman  2 , Harshit Garg  1 , Christian Jobin  3 , Teresa Johson-Pais  1 , Robin Leach  4 , Zhao Lai  5 , Michael A Liss  1
Affiliations

Prevalence of genotoxic bacteria in men undergoing biopsy for prostate cancer

John Lee et al. Prostate. 2023 May.

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.

Keywords: E. coli; genotoxin; prostate cancer; urinary microbiome.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST STATEMENT

The authors declare no conflict of interest.

Figures

FIGURE 1
FIGURE 1
Sensitivity and specificity of the multiplex PCR test for genotoxic bacteria. Multiplex PCR assay development. (A) Assay sensitivity: lane 1 positive control containing 140 CFU/mL, lane 2 positive control containing 70 CFU/mL, lane 3 positive control containing 28 CFU/mL, lane 4 positive control containing 14 CFU/mL, lane 5 positive control containing 2 CFU/mL, and lane 6 no DNA control. (B) Multiplex assay for marker specificity: lane 1 B1-7-6, lane 2 JJ0055, lane 3 JJ1166, lane 4 JJ1167, lane 5 positive Escherichia coli control for all four markers B1-5-1 and B3-1-4, and lane 6 no DNA control. (C) uidA controls: B1-7-6, lane 2 JJ0055, lane 3 JJ1166, lane 4 JJ1167, lane 5 positive B1-5-1 and B3-1-4, and lane 6 no DNA control. CFU, colony-forming unit; PCR, polymerase chain reaction. L, size ladder.
FIGURE 2
FIGURE 2
Validation consort diagram.
See this image and copyright information in PMC

References

    1. Helmink BA, Khan MAW, Hermann A, Gopalakrishnan V, Wargo JA. The microbiome, cancer, and cancer therapy. Nat Med. 2019;25: 377–388. - PubMed
    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;68:394–424. - PubMed
    1. Gao Y, Wei L, Wang C, et al. Chronic prostatitis alters the prostatic microenvironment and accelerates preneoplastic lesions in C57BL/6 mice. Biol Res. 2019;52:30. - PMC - PubMed
    1. Puhr M, De Marzo A, Isaacs W, et al. Inflammation, microbiota, and prostate cancer. Eur Urol Focus. 2016;2:374–382. - PubMed
    1. Correa P, Haenszel W, Cuello C, Tannenbaum S, Archer M. A model for gastric cancer epidemiology. Lancet. 1975;2:58–60. - PubMed

Publication types