Cancer Evo-Dev：炎症诱导的肿瘤发生理论

StephenW

Cancer Evo-Dev：炎症诱导的肿瘤发生理论
刘文斌1、杨登2、李子帅1、陈一凡1、朱晓琼3、谭小杰1、曹广文1
隶属关系
隶属关系

    1
    第二军医大学流行病学系，上海，中国。
    2
    山东第一医科大学公共卫生学院、山东省医学科学院，中国泰安。
    3
    安徽医科大学公共卫生学院营养系，合肥，中国。

    PMID：34880864 PMCID：PMC8645856 DOI：10.3389/fimmu.2021.768098

抽象的

慢性炎症是癌症发展的先决条件。在这里，我们基于目前对炎症相关致癌作用的理解，特别是乙型肝炎病毒慢性感染引起的肝癌发生，提出了一种称为癌症进化发展（Cancer Evo-Dev）的新理论框架。遗传易感性和环境暴露（例如病毒感染）之间的相互作用会维持慢性非消退性炎症。污染、代谢综合征、缺乏身体活动、衰老和不良的社会心理暴露也会通过诱导慢性低度闷烧炎症增加患癌症的风险。在非消退性炎症的微环境下，促炎因子通过诱导胞苷脱氨酶等致突变力与尿嘧啶-DNA糖基化酶等突变校正力之间的失衡，促进体细胞突变和病毒突变的产生。大多数具有体细胞突变和突变病毒的细胞在生存竞争中被淘汰。只有一小部分突变细胞存活下来，适应恶劣的环境，逆向分化，并通过改变信号通路发挥癌症起始细胞的作用。这些致癌细胞获得干性，重新编程代谢模式，并影响微环境。致癌过程遵循“突变-选择-适应”规律。慢性体力活动通过上调 NK 细胞和淋巴细胞的活性和数量以及延长白细胞端粒来降低炎症水平；下调促炎细胞因子，包括白细胞介素 6 和衰老的淋巴细胞，尤其是在老年人群中。抗炎药物可减少癌症的发生和复发。靶向癌症干性信号通路可能会导致癌症根除。 Cancer Evo-Dev 不仅有助于了解炎症促进癌症发展的机制，而且为各种癌症的有效预防和靶向治疗奠定了基础。

关键词：癌症；进化;炎;突变;病毒感染。

版权所有 © 2021 刘、邓、李、陈、朱、谭、曹。

StephenW

Cancer Evo-Dev: A Theory of Inflammation-Induced Oncogenesis
Wenbin Liu  1 , Yang Deng  2 , Zishuai Li  1 , Yifan Chen  1 , Xiaoqiong Zhu  3 , Xiaojie Tan  1 , Guangwen Cao  1
Affiliations
Affiliations

    1
    Department of Epidemiology, Second Military Medical University, Shanghai, China.
    2
    School of Public Health, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai'an, China.
    3
    Department of Nutrition, School of Public Health, Anhui Medical University, Hefei, China.

    PMID: 34880864 PMCID: PMC8645856 DOI: 10.3389/fimmu.2021.768098

Abstract

Chronic inflammation is a prerequisite for the development of cancers. Here, we present the framework of a novel theory termed as Cancer Evolution-Development (Cancer Evo-Dev) based on the current understanding of inflammation-related carcinogenesis, especially hepatocarcinogenesis induced by chronic infection with hepatitis B virus. The interaction between genetic predispositions and environmental exposures, such as viral infection, maintains chronic non-resolving inflammation. Pollution, metabolic syndrome, physical inactivity, ageing, and adverse psychosocial exposure also increase the risk of cancer via inducing chronic low-grade smoldering inflammation. Under the microenvironment of non-resolving inflammation, pro-inflammatory factors facilitate the generation of somatic mutations and viral mutations by inducing the imbalance between the mutagenic forces such as cytidine deaminases and mutation-correcting forces including uracil-DNA glycosylase. Most cells with somatic mutations and mutated viruses are eliminated in survival competition. Only a small percentage of mutated cells survive, adapt to the hostile environment, retro-differentiate, and function as cancer-initiating cells via altering signaling pathways. These cancer-initiating cells acquire stem-ness, reprogram metabolic patterns, and affect the microenvironment. The carcinogenic process follows the law of "mutation-selection-adaptation". Chronic physical activity reduces the levels of inflammation via upregulating the activity and numbers of NK cells and lymphocytes and lengthening leukocyte telomere; downregulating proinflammatory cytokines including interleukin-6 and senescent lymphocytes especially in aged population. Anti-inflammation medication reduces the occurrence and recurrence of cancers. Targeting cancer stemness signaling pathways might lead to cancer eradication. Cancer Evo-Dev not only helps understand the mechanisms by which inflammation promotes the development of cancers, but also lays the foundation for effective prophylaxis and targeted therapy of various cancers.

Keywords: cancer; evolution; inflammation; mutation; viral infection.

Copyright © 2021 Liu, Deng, Li, Chen, Zhu, Tan and Cao.

StephenW

https://www.frontiersin.org/arti ... mmu.2021.768098/pdf