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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.

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。

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