Farzaneh Dianatdar,1,*Mohammad Rabbani,2
1. Ph.D. Student of Microbiology, Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Sciences and Technology, University of Isfahan. 2. Associate Professor, Department of Cell and Molecular Biology & Microbiology, Faculty of Biological Sciences and Technology, University of Isfahan.
Introduction: Genetic, environmental and dietary factors have often been studied to induce cancer, and the effect of bacteria on cancer has been less studied. In the past, bacteria were not thought to cause cancer. William Russell first reported the effect of bacterial infection on carcinogenesis in 1890. In 1926, Thomas Glover was able to isolate bacteria from pleomorphic organism and help treat cancer patients with antibacterial serum. Other scientists, such as William Coley, Gunther Enderlein, Josef Issels, Royal Rife, Florence and Seibert continued their research. Bacteria cause cancer by two mechanisms, including chronic inflammation and the production of carcinogenic bacterial metabolites. Helicobacter pylori causes gastrointestinal cancer by causing chronic inflammation in the stomach. Inflammation caused by H. pylori induces cell proliferation and also produces mutant free radicals that cause cancer. H. pylori has been identified as the first cancer bacteria by the International Agency for Research on Cancer. H. pylori, Salmonella typhi, Streptococcus bovis and Chlamydia pneumoniae cause gastric, gallbladder, colorectal and lung cancers by different mechanisms. Salmonella typhi causes gallbladder cancer by producing typhoid toxin and damage to DNA and changes in the cell cycle. Porphyromonas gingivalis, Fusobacterium nucleatum, Treponema denticola and Streptococcus anginosus cause oral cancer by causing chronic inflammation, increased cell proliferation, suppression of the immune system and production of carcinogens. Bacteria can also be used to treat cancer. Live, attenuated or genetically modified bacteria or anaerobic bacteria such as Clostridium and Bifidobacterium can be selectively colonized in tumors and fight cancer cells.
Methods: 1. Parkin D. Cancers attributable to dietary factors in the UK in 2010 IV. Salt. British Journal of Cancer. 2011;105:S31-S3.
2. Dong Q-l, Xing X-y. Cancer cells arise from bacteria. Cancer cell international. 2018;18(1):1-9.
3. Sethi V, Vitiello GA, Saxena D, Miller G, Dudeja V. The role of the microbiome in immunologic development and its implication for pancreatic cancer immunotherapy. Gastroenterology. 2019;156(7):2097-115. e2.
4. Hanahan D, Weinberg RA. The hallmarks of cancer. cell. 2000;100(1):57-70.
5. Shalapour S, Karin M. Immunity, inflammation, and cancer: an eternal fight between good and evil. The Journal of clinical investigation. 2015;125(9):3347-55.
6. Galon J, Angell HK, Bedognetti D, Marincola FM. The continuum of cancer immunosurveillance: prognostic, predictive, and mechanistic signatures. Immunity. 2013;39(1):11-26.
7. Torres W, Lameda V, Olivar LC, Navarro C, Fuenmayor J, Pérez A, et al. Bacteria in cancer therapy: beyond immunostimulation. Journal of Cancer Metastasis and Treatment. 2018;4:4.
8. Crowe SE. Helicobacter infection, chronic inflammation, and the development of malignancy. Current opinion in gastroenterology. 2005;21(1):32-8.
9. Thøgersen R, Castro‐Mejía JL, Sundekilde UK, Hansen LH, Hansen AK, Nielsen DS, et al. Ingestion of an Inulin‐Enriched Pork Sausage Product Positively Modulates the Gut Microbiome and Metabolome of Healthy Rats. Molecular nutrition & food research. 2018;62(19):1800608.
10. Perillo F, Amoroso C, Strati F, Giuffrè MR, Díaz-Basabe A, Lattanzi G, et al. Gut microbiota manipulation as a tool for colorectal cancer management: recent advances in its use for therapeutic purposes. International Journal of Molecular Sciences. 2020;21(15):5389.
11. McCoy W, Mason 3rd J. Enterococcal endocarditis associated with carcinoma of the sigmoid; report of a case. Journal of the Medical Association of the State of Alabama. 1951;21(6):162-6.
12. Rommasi F. Bacterial-Based Methods for Cancer Treatment: What We Know and Where We Are. Oncology and Therapy. 2021:1-32.
13. Weber JR, Freyer D, Alexander C, Schröder NW, Reiss A, Küster C, et al. Recognition of pneumococcal peptidoglycan: an expanded, pivotal role for LPS binding protein. Immunity. 2003;19(2):269-79.
14. Song S, Vuai MS, Zhong M. The role of bacteria in cancer therapy–enemies in the past, but allies at present. Infectious agents and cancer. 2018;13(1):1-7.
15. Elagan SK, Almalki SJ, Alharthi M, Mohamed MS, El-Badawy MF. Role of bacteria in the incidence of common git cancers: the dialectical role of integrated bacterial DNA in human carcinogenesis. Infection and drug resistance. 2021;14:2003.
16. Koshiol J, Wozniak A, Cook P, Adaniel C, Acevedo J, Azócar L, et al. Salmonella enterica serovar Typhi and gallbladder cancer: a case–control study and meta‐analysis. Cancer medicine. 2016;5(11):3310-235.
17. Eyvazi S, Vostakolaei MA, Dilmaghani A, Borumandi O, Hejazi MS, Kahroba H, et al. The oncogenic roles of bacterial infections in development of cancer. Microbial pathogenesis. 2020;141:104019.
18. Cheng WT, Kantilal HK, Davamani F. The mechanism of Bacteroides fragilis toxin contributes to colon cancer formation. The Malaysian journal of medical sciences: MJMS. 2020;27(4):9.
19. Koeppel M, Garcia-Alcalde F, Glowinski F, Schlaermann P, Meyer TF. Helicobacter pylori infection causes characteristic DNA damage patterns in human cells. Cell reports. 2015;11(11):1703-13.
20. Ansari S, Yamaoka Y. Helicobacter pylori virulence factor cytotoxin-associated Gene A (CagA)-mediated gastric pathogenicity. International journal of molecular sciences. 2020;21(19):7430.
21. Riley DR, Sieber KB, Robinson KM, White JR, Ganesan A, Nourbakhsh S, et al. Bacteria-human somatic cell lateral gene transfer is enriched in cancer samples. PLoS Comput Biol. 2013;9(6):e1003107.
22. Morales A, Eidinger D, Bruce A. Intracavitary Bacillus Calmette-Guerin in the treatment of superficial bladder tumors. The Journal of urology. 1976;116(2):180-2.
23. Sieow BF-L, Wun KS, Yong WP, Hwang IY, Chang MW. Tweak to treat: reprograming bacteria for cancer treatment. Trends in Cancer. 2021;7(5):447-64.
24. Denny WA. Tumor-activated prodrugs—a new approach to cancer therapy. Cancer investigation. 2004;22(4):604-19.
Results: Pathogens cause cancer by producing carcinogens and inducing the immune system. Bacteria such as Fusobacterium spp, Borrelia burgdorferi, Escherichia coli, Mycoplasma spp, and Salmonella enterica can cause cancer. Bioengineering bacteria can also fight cancer by targeting cancer cells.
Conclusion: The hypothesis that the bacterial genome enters the human genome and causes cancer has not yet been confirmed and further studies are needed. Treatment of cancer with bacteria has disadvantages such as pathogenicity, negative interaction with chemical drugs and genetic changes of microbes.