Table 1.

The main mentioned cancers in this review and the usually observable and representative microbes and pathogenesis.

Cancers	Microbes	Possible pathogenic mechanisms
Prostate cancer	Mycoplasma genitalium	Infecting and inducing both symptomatic and asymptomatic inflammatory responses in the prostate (Yoon et al., 2012; Caini et al., 2014; Cavarretta et al., 2017); bacterial protein products, such as p37, that exert oncogenic effects (Ketcham et al., 2005; Goodison et al., 2007).
Lung cancer	Haemophilus influenzae, Enterobacter spp., Escherichia coli, Capnocytophaga and Veillonella, Streptococcus viridans, Firmicutes, TM7, Megasphaera, Granulicatella, Abiotrophia, Thermus, Streptococcus viridans, Legionella, tuberculosis	Microbial dysbiosis, genotoxicity and virulence effects, inflammation, immune responses, and metabolism (Weitzman and Gordon, 1990; Coussens and Werb, 2002; Ballaz and Mulshine, 2003; Roesler et al., 2012; Liu H. X. et al., 2018); chronic inflammation-associated carcinogenesis, with an increase in tumor necrosis factor and excessive and persistent local inflammation at sites of repair and fibrosis (Coussens and Werb, 2002; Ardies, 2003); low immunity (Christopoulos et al., 2014; Khoruts, 2018; Pandey et al., 2019); some metabolic-related signaling pathways, such as amino acid metabolism, carbohydrate metabolism, energy metabolism, and lipid metabolism (Gomes et al., 2019); upregulate the phosphoinositide 3-kinase pathway to participate in regulating cell proliferation, survival, and differentiation (Mendoza et al., 2011; Tsay et al., 2018); reduced signal transduction, increased excretory systems, amino acid metabolism, aldosterone-regulated sodium reabsorption, or amoebiasis pathways (Gomes et al., 2019); the cytokines might induce a cytokine cascade and a proliferation of the lung epithelial cells, the breaks in the chromosomal strands and the accumulation of DNA mutational changes might be eventually activated (Weitzman and Gordon, 1990; Ballaz and Mulshine, 2003); regional tumor peptides and even radiotherapy might lead to a microenvironment deregulation in granulomas (Christopoulos et al., 2014).
Pancreatic cancer	H. pylori, Fusobacterium, Lepotrichia, Malassezia	Activate selected toll-like receptors (TLR) in monocytic cells to generate a tolerogenic immune program, TLR2 and TLR5 ligation was demonstrated to induce innate and adaptive immune suppression to promote PDA (Pushalkar et al., 2018); the activation of the mannose-binding lectin–C3 cascade through the C3 complement pathway might cause inflammation induced by the oncogenic Kras, leading to fungal dysbiosis and promoting tumor progression (Aykut et al., 2019).
Colorectal cancer	Fusobacterium, Oribacterium, Prevotella, Citrobacter rodentium, Salmonella enterica, E.coli, Pseudomonas aeruginosa, Bacteroides fragilis, Campylobacter spp., E. Faecalis	Destroy the intestinal barrier, leading to the subsequent induction of pro-inflammatory cytokines, such as the reactive oxygen species (ROS), which promoted regeneration and predisposed to tumorigenesis (Kuraishy et al., 2011; Kux and Pitsouli, 2014; Li et al., 2019); Fusobacterium could bind to host epithelial Cadherin 1 through the adhesion of FadA and invade epithelial cells from through the E-cadherin/β-catenin signaling to induce inflammation and tumor cell growth in transformed cells (Rubinstein et al., 2013; Wong and Yu, 2019; Guo P. et al., 2020); enhance genomic instability both in two-dimensional and organotypic three-dimensional tissue models (Fearon, 2010); the deficiency in APC is associated with the sustained activation of the DNA damage response and the reduced capacity to repair different types of damage, including DNA breaks and oxidative damages. Infection with genotoxic Salmonella was shown to prevent cell cycle arrest in APC-deficient cells (Martin et al., 2019); The cytolethal distending toxin produced by Escherichia and Campylobacter spp. could induce double-strand DNA break via its deoxyribonuclease activity to develop cancer (Cuevas-Ramos et al., 2010; He et al., 2019); Colibactin produced by members of the Enterobacteriaceae family could also induce DNA strand break (Buc et al., 2013); B. fragilis toxin (Goodwin et al., 2011) and ROS produced by E. Faecalis were both associated with DNA damage and genomic instability in vitro (Huycke, 2002; Wang and Huycke, 2007); produce metabolites or genotoxins, such as cytolethal distending toxin and colibactin, some of them can be directly pro-carcinogenic or opportunistic microorganisms in the tumor-associated microenvironment. The cytolethal distending toxin produced by Escherichia and Campylobacter spp. (Cuevas-Ramos et al., 2010; He et al., 2019), Colibactin produced by members of the Enterobacteriaceae family (Buc et al., 2013), B. fragilis toxin (Goodwin et al., 2011), and ROS produced by E. Faecalis could induce the DNA strand break which might be associated with tumorigenesis (Huycke, 2002; Wang and Huycke, 2007); activate the pro-carcinogenic signaling pathways and result in molecular changes, ultimately leading to cancer (Wong and Yu, 2019; Zorron Cheng Tao Pu et al., 2019); interfere with signaling pathways to affect several cytokines and growth factors, such as IL-6, IL-2, and tumor necrosis factor, to control the process of regeneration in injured intestinal mucosa (Stavria and Yiorgos, 2013; Karin and Clevers, 2016); induce double-strand DNA breaks via its deoxyribonuclease activity to develop cancer (Cuevas-Ramos et al., 2010; He et al., 2019); the exposure of CRC cells to bacterial flagellin increased IL6 and CCL2/MCP-1 mRNA expression and IL6 excretion. Flagellin was shown to decrease caspase-1 activity and the production of reactive oxygen species to increase cytotoxicity in C26 cells, deteriorate the C2C12-myotubes, and decrease their numbers (Pekkala et al., 2019); the DNA damage was obviously enhanced in the mice colon epithelial cells (2012); Bacteroides fragilis promoted the IL-17 induction with early augmentation by pks+ E. coli cocolonization (2018); transform the tolerogenic apoptosis of ileal intestinal epithelial cells into immunogenic cell demise, then elicit IL-1β-dependent follicular T helper responses (Roberti et al., 2020); Chronic mucosal formation of IL17A produced by Th 17 cell might alter signaling pathways in colon epithelial cells or induce changes or mutations in DNA structure that facilitated the transformation of colon epithelial cells contributing to carcinogenesis (Hurtado et al., 2018); upregulated the spermine oxidase (SMOX) gene expression in human normal colon epithelial cells, the SMO protein played an important role in the alteration of polyamine metabolism, which catalyzed the oxidation of spermine to spermidine and produced hydrogen peroxide and aldehydes to result in apoptosis, DNA damage, and consequently the development of CRC (Pekkala et al., 2019); the intestinal infection with Pseudomonas aeruginosa with a latent oncogenic form of the Ras1 oncogene was found to lead to massive over-proliferation of intestinal cells through activating the c-Jun N-terminal kinase (JNK) pathway as a homeostatic compensatory mechanism to replenish the apoptotic enterocytes (Apidianakis et al., 2009). The Imd–dTab2–dTak1 innate immune pathway was converged with Ras1V12 signaling on JNK pathway activation to induce the basal invasion and distant spread of drosophila’s posterior intestinal cells (Bangi et al., 2013).
Gastric cancer	H. pylori, Lactic acid bacteria	The N-terminus of CagA could interreact with the tumor-suppressing protein and apoptosis-stimulating protein of p53 to subsequently disrupt the apoptotic function of the p53 tumor suppressor gene, which meant the possibility of progression to cancer was enhanced (Junaid et al., 2019); reduce the expression of the AU-rich element RNA-binding factor 1 via the CagA/p-ERK/AUF1 pathway to promote the incidence of gastric cancer (Guo Y. et al., 2020); the nucleotide transport and metabolism, amino acid transport and metabolism and the inorganic ion transport and metabolism were significantly abundant in the tumoral microbes (Liu et al., 2018); H. pylori penetrates the mucosal layer and settles on the surface of the gastric epithelial cells; releases toxic factors that damage the gastric epithelial cells; various inflammatory cells and mediators appear; produce immunoreactive substances, in addition to others (Goodwin, 1988). Lactic acid bacteria supply the exogenous lactate, which is a fuel source for cancer cells, promoting inflammation, angiogenesis, metastasis, epithelial-mesenchymal transition, immune evasion, production of reactive oxygen species and N-nitroso compounds (Vinasco et al., 2019).
HCC	H. pylori	The intrahepatic immune status and hemodynamics might be changed (Ki et al., 2010; Garcia et al., 2013; Okushin et al., 2018).
Cervical cancer	HPV, Fusobacterium spp., Chlamydia trachomatis, Atopobium vaginae, Dialister invisus, Finegoldia magna, Gardnerella vaginalis, Prevotella buccalis, P. timonensis	Modify the tumor-immune microenvironment through the E-cadherin/β-catenin signaling pathway to cause cancer (Audirac-Chalifour et al., 2016); induce Th2 immunity through the RORγτ+Treg cells, IL-10, and Th17 cells in the cervical epithelium (Punt et al., 2015).
Ovarian cancer	Chlamydia, Gemmata obscuriglobus, Halobacteroides halobius, Methyloprofundus sedimenti, Pediococcus, Pneumocystis, Acremonium, Cladophialophora, Malassezia, Microsporidia Pleistophora, Brucella, Mycoplasma	Inhibiting apoptosis, inducing the DNA damage response and increasing the susceptibility to other infections (Shanmughapriya et al., 2012); disrupt genetic stability (Kidane et al., 2014); gene members of the homologous recombination repair pathway might have frequent genetic and epigenetic alterations in ovarian cancer; the deficiency in homologous recombination repair was shown to induce genomic instability and a hyper-dependence on alternative DNA repair mechanisms and to enhance the sensitivity of double-strand break-inducing agents (Konstantinopoulos and Matulonis, 2018); the metabolic characteristics have been found to be changed in the tumors, including the enriched and reduced metabolism (Li, 2020).
Head and neck squamous cell carcinomas	Actinomycetes, Parvimonas, Tissierellaceae	Without the secreting protease inhibitors that inhibited tumorigenesis (Hozumi et al., 1972).
OSCC	Actinomyces (Actinobacteria), Firmicutes (Schwartzia and Selenomonas), Spirochaetes (Treponema), Porphyromonas gingivalis	Promote the overexpression of nuclear factor kappa-light-chain-enhancer of activated B cells and the activation of cyclin-D1, an epidermal growth factor receptor ligand that promote the growth of tumors, eventually provoking nuclear translocation; epithelial mesenchymal transformation in malignant cells, tumor proliferation and tumor invasion (Hoppe et al., 2016; Lafuente Ibanez de Mendoza et al., 2019).