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结直肠癌和泌尿系统癌症发病率的地理差异与人群暴露于产大肠杆菌素的大肠杆菌有关。

Geographical variation in the incidence of colorectal cancer and urinary tract cancer is associated with population exposure to colibactin-producing Escherichia coli.

作者信息

Mäklin Tommi, Taira Aurora, Arredondo-Alonso Sergio, Shao Yan, Stratton Michael R, Lawley Trevor D, Aaltonen Lauri A, Corander Jukka

机构信息

Department of Mathematics and Statistics University of Helsinki, Helsinki, Finland.

Department of Medical and Clinical Genetics University of Helsinki, Helsinki, Finland.

出版信息

Lancet Microbe. 2025 May;6(5):101015. doi: 10.1016/j.lanmic.2024.101015. Epub 2024 Dec 4.

DOI:10.1016/j.lanmic.2024.101015
PMID:39644909
Abstract

Biomedical research has implicated the bacterial metabolite colibactin as a causal risk factor for several cancer types, in particular, colorectal cancer. Colibactin has been known to drive tumorigenesis by inducing double-strand breaks in the DNA of epithelial cells exposed to colibactin-producing bacteria. Some phylogroup B2 Escherichia coli secrete colibactin during interbacterial warfare, concomitantly exposing the host to an increasing risk of DNA damage. This Personal View reviews the current knowledge about the cancer-colibactin interface and summarises metagenomics-based and population-genomics-based surveys to show that the prevalence of dominant colibactin-producing lineages of E coli varies considerably across geographical regions. The prevalence is further strongly associated with the age-standardised incidences of colorectal cancer, bladder cancer, and prostate cancer, suggesting that the degree of colibactin exposure in a population might contribute to the geographical variation of these cancers. Our observations provide a strong impetus for further research and the development of novel interventions to reduce the risks for colibactin-related cancers.

摘要

生物医学研究表明,细菌代谢产物大肠杆菌素是多种癌症类型(尤其是结直肠癌)的致病风险因素。已知大肠杆菌素通过在暴露于产生大肠杆菌素的细菌的上皮细胞DNA中诱导双链断裂来驱动肿瘤发生。一些B2系统发育群的大肠杆菌在细菌间战争期间分泌大肠杆菌素,同时使宿主面临DNA损伤风险增加的情况。这篇个人观点文章回顾了关于癌症与大肠杆菌素关系的现有知识,并总结了基于宏基因组学和基于群体基因组学的调查,以表明大肠杆菌主要产大肠杆菌素谱系的流行率在不同地理区域有很大差异。这种流行率还与结直肠癌、膀胱癌和前列腺癌的年龄标准化发病率密切相关,这表明人群中大肠杆菌素的暴露程度可能导致这些癌症的地理差异。我们的观察结果为进一步研究以及开发新的干预措施以降低与大肠杆菌素相关癌症的风险提供了强大动力。

相似文献

1
Geographical variation in the incidence of colorectal cancer and urinary tract cancer is associated with population exposure to colibactin-producing Escherichia coli.结直肠癌和泌尿系统癌症发病率的地理差异与人群暴露于产大肠杆菌素的大肠杆菌有关。
Lancet Microbe. 2025 May;6(5):101015. doi: 10.1016/j.lanmic.2024.101015. Epub 2024 Dec 4.
2
Carriage of Colibactin-producing Bacteria and Colorectal Cancer Risk.产 Colibactin 菌的携带情况与结直肠癌风险。
Trends Microbiol. 2020 Nov;28(11):874-876. doi: 10.1016/j.tim.2020.05.015. Epub 2020 Jun 5.
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Mother-to-infant transmission of the carcinogenic colibactin-producing bacteria.产致癌性大肠杆菌素细菌的母婴传播。
BMC Microbiol. 2021 Aug 24;21(1):235. doi: 10.1186/s12866-021-02292-1.
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E. coli and colorectal cancer: a complex relationship that deserves a critical mindset.大肠杆菌与结直肠癌:一种值得批判性思维的复杂关系。
Crit Rev Microbiol. 2018 Sep;44(5):619-632. doi: 10.1080/1040841X.2018.1481013. Epub 2018 Jun 17.
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Characterization of Colibactin-Producing Escherichia coli Isolated from Japanese Patients with Colorectal Cancer.从日本结直肠癌患者中分离的产 Colibactin 大肠埃希菌的特性研究。
Jpn J Infect Dis. 2020 Nov 24;73(6):437-442. doi: 10.7883/yoken.JJID.2020.066. Epub 2020 May 29.
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Colibactin possessing E. coli isolates in association with colorectal cancer and their genetic diversity among Pakistani population.与结直肠癌相关的具有 colibactin 的大肠杆菌分离株及其在巴基斯坦人群中的遗传多样性。
PLoS One. 2022 Nov 11;17(11):e0262662. doi: 10.1371/journal.pone.0262662. eCollection 2022.
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In vitro genotoxicity analyses of colibactin-producing E. coli isolated from a Japanese colorectal cancer patient.从一名日本结直肠癌患者中分离出的产 colibactin 大肠杆菌的体外遗传毒性分析。
J Toxicol Sci. 2019;44(12):871-876. doi: 10.2131/jts.44.871.
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Escherichia coli ClbS is a colibactin resistance protein.大肠杆菌ClbS是一种大肠杆菌素抗性蛋白。
Mol Microbiol. 2016 Mar;99(5):897-908. doi: 10.1111/mmi.13272. Epub 2015 Dec 1.
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Small-molecule inhibitors prevent the genotoxic and protumoural effects induced by colibactin-producing bacteria.小分子抑制剂可预防产 Colibactin 细菌引起的遗传毒性和促肿瘤作用。
Gut. 2016 Feb;65(2):278-85. doi: 10.1136/gutjnl-2014-307241. Epub 2015 Jan 14.
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The Colibactin Genotoxin Generates DNA Interstrand Cross-Links in Infected Cells.产 Colibactin 遗传毒素在感染细胞中产生 DNA 链间交联。
mBio. 2018 Mar 20;9(2):e02393-17. doi: 10.1128/mBio.02393-17.

引用本文的文献

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Gut microbiota interplay with autophagy-EMT dynamics in colorectal cancer.肠道微生物群与结直肠癌中的自噬-上皮-间质转化动态相互作用。
Front Cell Dev Biol. 2025 Aug 21;13:1608248. doi: 10.3389/fcell.2025.1608248. eCollection 2025.
2
Colibactin genes are highly prevalent in the developing infant gut microbiome.大肠杆菌素基因在发育中的婴儿肠道微生物群中高度普遍。
medRxiv. 2025 Aug 13:2025.08.12.25333511. doi: 10.1101/2025.08.12.25333511.
3
Microbial molecules, metabolites, and malignancy.微生物分子、代谢产物与恶性肿瘤
Neoplasia. 2025 Feb;60:101128. doi: 10.1016/j.neo.2025.101128. Epub 2025 Jan 18.