The Relationship Between Toxoplasmosis and Prostate Cancer Patients

• Raghad N. Shihab

  Iraqi Centre for Cancer and Medical Genetic Research, Mustansiriyah University

• Evan H. Sulaiman

  Applied Pathological Analysis College of Science Al-Nahrain University

• Atheer Abd elqader Zain El Abdeen

  Iraqi Centre for Cancer and Medical Genetic Research, Mustansiriyah University

Background: Toxoplasmosis is one of the most common global life-threatening diseases among immunocompromised persons. It is not only a disease, but also a contributing factor to several pathological disorders, such as prostate cancer. Objectives. The purpose of the presented work is determining the prevalence regarding toxoplasmosis in Iraqi cancer patients and to connect that prevalence with the type of malignancy. Patients and Methods: This study included 115 male patients (75 with prostatic tumors and 40 with normal prostate glands) from Al-Amal National Hospital for Cancer Management was enrolled between December 15, 2023and July 1, 2024. Results: The study's results showed that prostate cancer patient group with the toxoplasmosis had the greatest IgG antibody level, measuring 52.64±1.16 UI/ml. The control group had 0.306±0.05 UI/ml. According to CMIA, all groups had seronegative IgM antibody levels. However, the mean PSA of the patients in this study was 66.72±0.51 ng/ml, compared to 2.48 ±0.04 ng/ml for the healthy control groups. Measuring IL-10 levels in samples were done by ELISA method showed a group of prostate cancer patients with toxoplasmosis has highest level 19.36 ±0.15 pg/ml, while the healthy control group has the lowest level of the same assay 12.78 ±0.13 pg/ml. However, illustrated that prostate cancer patient group with toxoplasmosis higher level significantly (P≤0.01) of IFNγ in comparation of the group of healthy control. Conclusion: Prostate inflammation is caused by the common parasite T. gondii, which encysts and causes chronic inflammation in prostate of any species, according to this work. The anti-inflammatory cytokines IL-10 and IFNγ were linked to an increased risk of prostate cancer infected with toxoplasmosis.

Highlights:

1. Toxoplasmosis contributes to prostate cancer risk via chronic inflammation.
2. Analyzed IgG, PSA, IL-10, and IFNγ in prostate cancer patients.
3. Elevated IL-10, IFNγ indicate toxoplasmosis increases prostate cancer susceptibility.

Keywords: Toxoplasma gondii; IgM, IgG, Prostate cancer

R. N. Shihab and I. K. Al-Aubaidi, "Toxoplasmosis in Thalassemic Iraqi Patients: Serological and Hematological Study," Romanian Journal of Infectious Diseases, vol. 27, no. 2, pp. 97–103, 2024.

D. L. Colinot, et al., "The Common Parasite Toxoplasma Gondii Induces Prostatic Inflammation and Microglandular Hyperplasia in a Mouse Model," The Prostate, vol. 77, no. 10, pp. 1066–1075, 2017.

R. An, et al., "Encephalitis Is Mediated by ROP18 of Toxoplasma Gondii, a Severe Pathogen in AIDS Patients," Proceedings of the National Academy of Sciences, vol. 115, no. 23, pp. E5344–E5352, 2018.

Y. Wang, et al., "Evaluation of Liquid from the Papanicolaou Test and Other Liquid Biopsies for the Detection of Endometrial and Ovarian Cancers," Science Translational Medicine, vol. 10, no. 433, 2018, Art. no. eaap8793.

J. Mayoral, et al., "Toxoplasma Gondii PPM3C, a Secreted Protein Phosphatase, Affects Parasitophorous Vacuole Effector Export," PLoS Pathogens, vol. 16, no. 12, 2020, Art. no. e1008771.

E. J. Jones, T. Korcsmaros, and S. R. Carding, "Mechanisms and Pathways of Toxoplasma Gondii Transepithelial Migration," Tissue Barriers, vol. 5, no. 1, 2017, Art. no. e1273865.

A. Imam, et al., "Serologic Evidence of Toxoplasma Gondii Infection Among Cancer Patients: A Prospective Study From Qassim Region, Saudi Arabia," Saudi Medical Journal, vol. 38, no. 3, pp. 319–324, 2017.

G. Lu, et al., "Transcriptome Sequencing Investigated the Tumor-Related Factors Changes After T. Gondii Infection," Frontiers in Microbiology, vol. 10, 2019, Art. no. 181.

J. P. Dubey, et al., "Congenital Toxoplasmosis in Humans: An Update of Worldwide Rate of Congenital Infections," Parasitology, vol. 148, no. 12, pp. 1406–1416, 2021.

H. Sung, et al., "Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries," CA: A Cancer Journal for Clinicians, vol. 71, no. 3, pp. 209–249, 2021.

M. M. Alani, "Serum Interleukin 1 and Interleukin 10 Levels in Iraqi Leukemic Patients With Hepatitis G Virus Infection," Journal of the Faculty of Medicine Baghdad, vol. 54, no. 4, pp. 340–344, 2012.

E. H. Wilson, et al., "A Critical Role for IL-10 in Limiting Inflammation During Toxoplasmic Encephalitis," Journal of Neuroimmunology, vol. 165, nos. 1–2, pp. 63–74, 2005.

R. N. Shihab and I. K. Al-Aubaidi, "Regulatory Role of Interleukin 10 in Iraqi Thalassemic Patients Infected With Toxoplasmosis," CommPrac Journal, vol. 20, no. 6, pp. 97–102, 2023.

Y.-I. Jeong, et al., "Induction of IL-10-Producing Regulatory B Cells Following Toxoplasma Gondii Infection Is Important to the Cyst Formation," Biochemistry and Biophysics Reports, vol. 7, pp. 91–97, 2016.

F. Thomas, et al., "Incidence of Adult Brain Cancers Is Higher in Countries Where the Protozoan Parasite Toxoplasma Gondii Is Common," Biology Letters, vol. 8, no. 1, pp. 101–103, 2012.

C. Lang, U. Groß, and C. G. K. Lüder, "Subversion of Innate and Adaptive Immune Responses by Toxoplasma Gondii," Parasitology Research, vol. 100, pp. 191–203, 2007.

C. Yoon, et al., "Exploring the Potential of Toxoplasma Gondii in Drug Development and as a Delivery System," Experimental & Molecular Medicine, vol. 56, no. 2, pp. 289–300, 2024.

L. B. Ivashkiv, "IFNγ: Signalling, Epigenetics and Roles in Immunity, Metabolism, Disease and Cancer Immunotherapy," Nature Reviews Immunology, vol. 18, no. 9, pp. 545–558, 2018.

J. D. Burke and H. A. Young, "IFN-γ: A Cytokine at the Right Time, Is in the Right Place," Seminars in Immunology, vol. 43, 2019.

SAS Institute Inc., Statistical Analysis System, User's Guide. Version 9, 6th ed., Cary, NC, USA, 2021.

I. K. Al-Aubaidi, S. A. Saeed, and A. I. Jaaffar, "Blood lymphocytes detection in Iraqi diabetic type 2 patients infected with chronic toxoplasmosis by using flow cytometry," Indian J. Forensic Med. Toxicol., vol. 14, no. 4, pp. 2297–2303, 2020.

K. M. Mustafa, A. B. Mohammed, and W. M. S. Mero, "Seroprevalence of Toxoplasma gondii antibodies and associated risk factors among women in Zakho City, Iraq," Cureus, vol. 16, no. 3, 2024.

N. Bouscaren, et al., "Prevalence of toxoplasmosis and its association with dementia in older adults in Central Africa: A result from the EPIDEMCA programme," Trop. Med. Int. Health, vol. 23, no. 12, pp. 1304–1313, 2018.

M. Nikiforou, et al., "Prostate cancer in a 63-year-old man: A case report," J. Oncol. Res. Forecast., vol. 1, no. 1, 2018, Art. no. 1001.

S. N. M. Al-Doury, "Effect of Toxoplasma gondii on alteration of gene sequence in prostate cancer patients," Biochem. Cell. Arch., vol. 19, no. 1, 2019.

J. Seladi-Schulman, "Everything you need to know about toxoplasmosis," News Lett., vol. 12, 2018.

N. S. Mohammed, "The effect of Toxoplasma gondii on DNA sequence alteration among breast cancer patients," Iraqi Nat. J. Nurs. Specialties, vol. 30, no. 2, 2017.

D. A. Abdullah, "The level of cytokines IL-4, IL-12p40, IFN-γ during acute toxoplasmosis," J. Fac. Med. Baghdad, vol. 53, no. 4, pp. 408–413, 2011.

M. M. Moretto, S. Hwang, and I. A. Khan, "Downregulated IL-21 response and T follicular helper cell exhaustion correlate with compromised CD8 T cell immunity during chronic toxoplasmosis," Front. Immunol., vol. 8, 2017, Art. no. 1436.

S. M. Mahmoud, Z. S. E. Abass, and N. A. Jafar, "The use of interleukin-10 as a biomarker for diagnosis of viral hepatitis type C infections and related liver function in beta-thalassemic major patients," J. Madenat Alelem Univ. Coll., vol. 10, no. 1, pp. 10–25, 2018.

K. Nagata and C. Nishiyama, "IL-10 in mast cell-mediated immune responses: Anti-inflammatory and proinflammatory roles," Int. J. Mol. Sci., vol. 22, no. 9, 2021, Art. no. 4972.

W. Ouyang and A. O’Garra, "IL-10 family cytokines IL-10 and IL-22: From basic science to clinical translation," Immunity, vol. 50, no. 4, pp. 871–891, 2019.

M. H. Mannino, et al., "The paradoxical role of IL-10 in immunity and cancer," Cancer Lett., vol. 367, no. 2, pp. 103–107, 2015.

M.-H. Wang, et al., "Association of IL10 and other immune response- and obesity-related genes with prostate cancer in CLUE II," Prostate, vol. 69, no. 8, pp. 874–885, 2009.

J. M. Faupel-Badger, et al., "Association of IL-10 polymorphisms with prostate cancer risk and grade of disease," Cancer Causes Control, vol. 19, pp. 119–124, 2008.

T. Men, et al., "The impact of interleukin-10 (IL-10) gene 4 polymorphisms on peripheral blood IL-10 variation and prostate cancer risk based on published studies," Oncotarget, vol. 8, no. 28, pp. 45994–46001, 2017.

H.-H. Lee, et al., "Removal of N-linked glycosylation enhances PD-L1 detection and predicts anti-PD-1/PD-L1 therapeutic efficacy," Cancer Cell, vol. 36, no. 2, pp. 168–178, 2019.

S. Zhang, et al., "Systemic interferon-γ increases MHC class I expression and T-cell infiltration in cold tumors: Results of a phase 0 clinical trial," Cancer Immunol. Res., vol. 7, no. 8, pp. 1237–1243, 2019.