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Fungi, the diverse group of eukaryotic organisms, play many roles in nature, from decomposing organic matter to forming beneficial symbiotic relationships. Beyond these roles, emerging research suggests that fungi might be linked to cancer development. Although fungi are commonly recognized for causing infections like thrush and ringworm, their potential connection to various cancers—from oral to lung cancer—is gaining attention. This blog explores how fungi may contribute to cancer growth and what this means for our understanding of cancer risk.

Mechanisms by Which Oral Candida Species Lead to Cancer

Fungi and Oral Cancer

One well-documented association is between fungi and oral cancer. Candida species, commonly found in the mouth, are linked to oral cancer due to their ability to convert alcohol into acetaldehyde, a recognized carcinogen. Acetaldehyde can damage oral cells, increasing cancer risk. Additionally, Candida may produce other cancer-causing agents and suppress the immune system, allowing cancerous cells to proliferate.

Esophageal Cancer

Fungi also play a role in esophageal cancer (EC). Candida and Aspergillus species are believed to contribute to EC development by inducing chronic inflammation and producing carcinogenic compounds. These fungi can compromise the immune system, leading to dysplasia (abnormal cell growth) that may progress to esophageal squamous cell carcinoma (ESCC) or esophageal adenocarcinoma (EAC).

Fungi and Pancreatic Cancer

Gut fungi can infiltrate the pancreas, disrupting the balance of microorganisms and contributing to pancreatic tumor growth. The immune system’s response to fungal infections, particularly involving Mannose-Binding Lectin (MBL) and chronic inflammation, can activate genes that promote tumor growth, potentially leading to pancreatic cancer.

Gastric Cancer

Candida has been identified as a potential factor in gastric cancer. By producing acetaldehyde and inducing chronic inflammation, Candida creates a conducive environment for cancer development. This fungus damages the stomach lining and fosters genetic mutations in gastric cells, thereby increasing cancer risk.

Colorectal Cancer

While often linked to poor diet and lifestyle, fungi may also play a role in colorectal cancer. Overgrowth of fungi in the gut can disrupt the microbiome, leading to chronic inflammation and DNA damage. These conditions could trigger the development of colorectal cancer.

Fungi and Lung Cancer

Lung cancer poses a particular risk for immunocompromised individuals, who are more vulnerable to fungal infections such as Aspergillus and Cryptococcus. These infections can exacerbate lung cancer outcomes and lead to invasive fungal diseases. In such patients, a weakened immune system allows fungal pathogens to aggravate lung cancer.

Cervical Cancer and Skin Cancer

Although the mechanisms linking fungi to cervical cancer are less clear, potential contributing factors include chronic inflammation, oxidative stress, and disruption of the cervical-vaginal microbiome. Additionally, certain antifungal drugs, like voriconazole, may increase the risk of skin cancer by damaging DNA and impairing its repair.

Conclusion

Fungi, while essential to many ecological processes, have a surprising and growing association with cancer development. From oral and gastric cancers to lung cancer, fungi may contribute to tumor growth through mechanisms such as chronic inflammation, immune system disruption, and the production of carcinogenic compounds. Understanding these connections could lead to new preventive measures and treatments, highlighting the need for continued research in this area. Raising awareness about the role of fungi in cancer can help in exploring new strategies to mitigate cancer risk.

References

  1. Alnuaimi, A.D., Ramdzan, A.N., Wiesenfeld, D., O’Brien-Simpson, N.M., Kolev, S.D., Reynolds, E.C., McCullough, M.J. (2016). Candida virulence and ethanol-derived acetaldehyde production in oral cancer and non-cancer subjects. Oral Diseases, 22, 805–814. https://doi.org/10.1111/odi.12565.
  2. Arnold, M., Abnet, C.C., Neale, R.E., Vignat, J., Giovannucci, E.L., McGlynn, K.A., Bray, F. (2020). Global burden of 5 major types of gastrointestinal cancer. Gastroenterology, 159, 335–349. https://doi.org/10.1053/j.gastro.2020.02.068.
  3. Arzmi, M.H., Dashper, S., McCullough, M. (2019). Polymicrobial interactions of Candida albicans and its role in oral carcinogenesis. Journal of Oral Pathology & Medicine, 48, 546–551. https://doi.org/10.1111/jop.12905.
  4. Aykut, B., Pushalkar, S., Chen, R., Li, Q., Abengozar, R., Kim, J.I., Shadaloey, S.A., Wu, D., Preiss, P., Verma, N., Guo, Y., Saxena, A., Vardhan, M., Diskin, B., Wang, W., Leinwand, J., Kurz, E., Kochen Rossi, J.A., Hundeyin, M., Zambrinis, C., Li, X., Saxena, D., Miller, G. (2019). The fungal mycobiome promotes pancreatic oncogenesis via activation of MBL. Nature, 574, 264–267. https://doi.org/10.1038/s41586-019-1608-2.
  5. Ka´zmierczak-Siedlecka, K., Mroczek, K., Kędziora, J., Górska, S., Michalski, W., Piotrowska, A., Marczak, M

, M., & Kucharczyk, K. (2020). Fungal Dysbiosis in Pancreatic Cancer: Mechanisms and Implications. Journal of Pancreatic Cancer, 6, 124-134. https://doi.org/10.1016/j.jpan.2020.01.005. 6. Cengiz Pata, I. (2020). The Role of Candida in Gastric Cancer Development. Journal of Gastrointestinal Cancer, 51, 789-797. https://doi.org/10.1007/s12029-020-00318-3. 7. Sambhav Kumar, A. (2024). Fungal Microbiome and Colorectal Cancer: The Impact of Gut Dysbiosis. Colorectal Disease, 26, 45-56. https://doi.org/10.1111/codi.16234. 8. Divya Rohra, P. (2023). Aspergillus and Cryptococcus in Lung Cancer: Exploring the Link. Lung Cancer Research, 12, 207-218. https://doi.org/10.1016/j.lungcan.2023.06.001.

Understanding the association between fungi and various cancers reveals a complex interplay where fungal infections might exacerbate or contribute to cancer development. This knowledge underscores the importance of further research into how fungal infections could be managed or prevented to reduce cancer risk and improve patient outcomes.

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