Polymorphism of Free Radicals Detoxification Genes GSTM1 and GSTT1 is Associated to Prostate Cancer Risk in men: Case Study in Benin

Firmin H. Sagbo^{1, 2}, M. Mènonvè Atindehou^{1, 2}, Haboubacar Elhadji Yaou Moussa^{1, 3}, Sara Y. Houngue^{1, 3}, Josué Avakoudjo⁴, Lucie Ayi-fanou^{1, 2} and Callinice D. Capo-chichi^{1, 3,}

¹Unit of Biochemistry and Molecular Biology/Laboratory of Biochemistry, Molecular Biology and Environment/Faculty of Sciences and Techniques/University of Abomey-Calavi, Cotonou 04 BP 0320, Benin

²Laboratory of Biochemistry, Molecular Biology and Environment

³Laboratoire des Biomarqueurs Moléculaires en Cancérologie et Nutrition

⁴National University Teaching Hospital (CNHU-HKM), Cotonou Benin

Cite this paper:
Firmin H. Sagbo, M. Mènonvè Atindehou, Haboubacar Elhadji Yaou Moussa, Sara Y. Houngue, Josué Avakoudjo, Lucie Ayi-fanou and Callinice D. Capo-chichi. Polymorphism of Free Radicals Detoxification Genes GSTM1 and GSTT1 is Associated to Prostate Cancer Risk in men: Case Study in Benin. American Journal of Cancer Prevention. 2023; 10(1):21-27. doi: 10.12691/ajcp-10-1-5

Abstract

Background: Most diseases including cancers are subsequent to the imbalance between oxidation and reduction in cells. Glutathione-s-transferases (GSTM1 and GSTT1) are cell detoxification enzymes which are involved in the conversion of free radicals derived from reduced oxygen (known to harm DNA) in oxidized molecules which are not harmful for the DNA. Cells with deficient GSTM1 or GSTT1 activity, have impaired cellular detoxification which exposed them to free radicals derived from environment, unhealthy nutrition, or some drugs, all of which can harm DNA and cause genomic instability leading to cancer. Hence, their implication in cancers affecting men in Benin was not investigated and needs to be addressed. The aim of this study is to assess the association between the loss of GSTM1 and GSTT1 and prostate cancer in Benin. Methods: GSTM1 and GSTT1 analyses were done with blood samples of prostate cancer patients and pseudo healthy individuals exposed to environmental pollutions. For this pilot study, a questionnaire was used to recruit 53 prostate cancer patients and 53 pseudo-healthy motorized bike drivers as well as matching healthy controls (already published elsewhere). Signed informed consent was collected before peripheral blood withdrawal in a 5 ml EDTA tube. DNA extraction was carried out in the laboratory with the phenol/chloroform method. The Multiplex polymerase chain reaction (PCR) was used to amplify and detect the presence of GSTM1 and GSTT1. Results: Our results showed that prostate cancer was more predominant in elderly men 60-80 years than 40-59 years (p <0.001), and the majority of cancer patients were uneducated (62%). We have also noticed that most of them were polygamous (78%) and reside in urban areas. No significant association was observed between the loss of GSTM1 or GSTT1 and prostate cancer. However, the combined losses of GSTM1 and GSTT1 showed a significant association with prostate cancer (P<0.05). However, we have noticed more deletion of GSTT1 in prostate cancer. Conclusion: Overall, our study determines that the impairment of GSTM1 and GSTT1 is associated with prostate cancer. Thus, the deficiency of GSTM1 and GSTT1 could be used as a predictive biomarker of predisposition to cancers including prostate.

Keywords:
Prostate Cancer Glutathione-S-transferases detoxification gene multiplex PCR

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Rybka, A. (2020). Neoplastic diseases (cancer) of occupational origine between 2003-2019 in Podkarpackie voivodeship. Przeglad epidemiologiczny, 74, 483‑491.
[2]	Kolak, A., Kamińska, M., Sygit, K., Budny, A., Surdyka, D., Kukiełka-Budny, B., & Burdan, F. (2017). Primary and secondary prevention of breast cancer. Annals of Agricultural and Environmental Medicine: AAEM, 24(4), 549‑553.
[3]	Sung, H., Ferlay, J., Siegel, R. L., Laversanne, M., Soerjomataram, I., Jemal, A., & Bray, F. (2021). Global Cancer Statistics 2020 : GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians, 71(3), 209‑249.
[4]	Ferlay, J., Colombet, M., Soerjomataram, I., Parkin, D. M., Piñeros, M., Znaor, A., & Bray, F. (2021). Cancer statistics for the year 2020 : An overview. International Journal of Cancer.
[5]	Abbasi-Kangevari, M., Saeedi Moghaddam, S., Ghamari, S.-H., Azangou-Khyavy, M., Malekpour, M.-R., Rezaei, N., Rezaei, N., Kolahi, A.-A., GBD 2019 NAME Prostate Cancer Collaborators, Amini, E., Mokdad, A. H., Jamshidi, H., Naghavi, M., Larijani, B., & Farzadfar, F. (2022). The burden of prostate cancer in North Africa and Middle East, 1990-2019 : Findings from the global burden of disease study. Frontiers in Oncology, 12, 961086.
[6]	Didkowska, J., Wojciechowska, U., Michalek, I. M., & Caetano dos Santos, F. L. (2022). Cancer incidence and mortality in Poland in 2019. Scientific Reports, 12(1), Article 1.
[7]	Gliniewicz, A., Dudek-Godeau, D., & Bielska-Lasota, M. (2020). Survival in men diagnosed with prostate cancer in Poland in the years 2000—2014 compared to European Countries based on Concord-3. Roczniki Panstwowego Zakladu Higieny, 71(4), 445‑453.
[8]	Yevi, D. M. I., Hodonou, F., Sossa, J., Amegayibor, O., Akoha, J., Agounkpe, M. M., Natchagande, G., & Avakoudjo, J. D. G. (2018). Diagnostic du cancer de la prostate a Cotonou : A propos de 109 cas. Journal de La Recherche Scientifique de l’Université de Lomé, 20(3), Article 3.
[9]	Gnangnon, F., Egue, M., Akele-Akpo, M., Amidou, S., Brun, L., Mehinto, D., Houinato, D., & Parkin, D. (2020a). Incidence des cancers à Cotonou entre 2014–2016 : Les premiers résultats du premier registre des cancers en République du Bénin. Revue d’Épidémiologie et de Santé Publique, 68, S124.
[10]	Haboubacar Elhadji Yaou Moussa, Maazou Halidou, Sara Y. Houngue, Josué Avakoudjo, Solomon Oladapo Rotimi, and Callinice D. Capo-Chichi, “The prediagnosis of prostate cancer risk is possible with the evaluation of BRCA1 primary exons in men.” American Journal of Cancer Prevention, vol. 10, no. 1 (2023): 14-20.
[11]	Messina, C., Cattrini, C., Soldato, D., Vallome, G., Caffo, O., Castro, E., Olmos, D., Boccardo, F., & Zanardi, E. (2020). BRCA Mutations in Prostate Cancer : Prognostic and Predictive Implications. Journal of Oncology, 2020, 4986365.
[12]	Barnes, D. R., Silvestri, V., Leslie, G., McGuffog, L., Dennis, J., Yang, X., Adlard, J., Agnarsson, B. A., Ahmed, M., Aittomäki, K., Andrulis, I. L., Arason, A., Arnold, N., Auber, B., Azzollini, J., Balmaña, J., Barkardottir, R. B., Barrowdale, D., Barwell, J., Consortium of Investigators of Modifiers of BRCA1 and BRCA2. (2022). Breast and Prostate Cancer Risks for Male BRCA1 and BRCA2 Pathogenic Variant Carriers Using Polygenic Risk Scores. Journal of the National Cancer Institute, 114(1), 109‑122.
[13]	Stone, L. (2019). The IMPACT of BRCA2 in prostate cancer. Nature Reviews Urology, 16(11), Article 11.
[14]	Miao, L.-F., Wang, X.-Y., Ye, X.-H., Cui, M.-S., & He, X.-F. (2019). Combined effects of GSTM1 and GSTT1 polymorphisms on breast cancer risk : A MOOSE-compliant meta-analysis and false-positive report probabilities test. Medicine, 98(6), e14333.
[15]	Wu, B., & Dong, D. (2012). Human cytosolic glutathione transferases : Structure, function, and drug discovery. Trends in Pharmacological Sciences, 33(12), 656‑668.
[16]	Prysyazhnyuk, V., Sydorchuk, L., Sydorchuk, R., Prysiazhniuk, I., Bobkovych, K., Buzdugan, I., Dzuryak, V., & Prysyazhnyuk, P. (2021). Glutathione-S-transferases genes-promising predictors of hepatic dysfunction. World Journal of Hepatology, 13(6), 620‑633.
[17]	Oakley, A. (2011a). Glutathione transferases : A structural perspective. Drug Metabolism Reviews, 43(2), 138‑151.
[18]	Oakley, A. (2011b). Glutathione transferases : A structural perspective. Drug Metabolism Reviews, 43(2), 138‑151.
[19]	Wilkinson J, Clapper ML. Detoxication enzymes and chemoprevention. Proc Soc Exp Biol Med Soc Exp Biol Med N Y N. nov 1997;216(2):192‑200.
[20]	Zhang W, van Gent DC, Incrocci L, van Weerden WM, Nonnekens J. Role of the DNA damage response in prostate cancer formation, progression and treatment. Prostate Cancer Prostatic Dis [Internet]. mars 2020 [cité 21 juin 2023];23(1):24‑37. Disponible sur:
[21]	Sagbo F, Lawin HB, Atindehou M, Anago EA, Goyito M, Cachon B, et al. Effects of BTEX Exposure on Hematological and C-Reactive-Protein in Professional and Non Professional Motorcycle Drivers in Cotonou/Benin. J Environ Pollut Hum Health [Internet]. 16 déc 2019 [cité 21 juin 2023];8(1):1‑5. Disponible sur:
[22]	Gautam, A. (2022). Phenol-Chloroform DNA Isolation Method. In A. Gautam (Éd.), DNA and RNA Isolation Techniques for Non-Experts (p. 33‑39). Springer International Publishing.
[23]	Ghiasi, M., Safinejad, K. and Mirfakhraie, R. (2017) Study of Glutathione-S-Transferase (gstm1 and gstt1) Gene Polymorphisms in Down Syndrome Patients. MOJ Women’s Health, 6, 361-364.
[24]	Liu, D., Liu, Y., Ran, L., Shang, H., & Li, D. (2013). GSTT1 and GSTM1 polymorphisms and prostate cancer risk in Asians : A systematic review and meta-analysis. Tumour Biology: The Journal of the International Society for Oncodevelopmental Biology and Medicine, 34(5), 2539‑2544.
[25]	Liu, D., Che, B., Chen, P., He, J., Mu, Y., Chen, K., Zhang, W., Xu, S., & Tang, K. (2022a). GSTT1, an increased risk factor for prostate cancer in patients with metabolic syndrome. Journal of Clinical Laboratory Analysis, 36(4), e24352.
[26]	Journée mondiale contre le cancer 2023. (2023, février 2). OMS | Bureau régional pour l’Afrique.
[27]	Liu, D., Che, B., Chen, P., He, J., Mu, Y., Chen, K., Zhang, W., Xu, S., & Tang, K. (2022b). GSTT1, an increased risk factor for prostate cancer in patients with metabolic
[28]	Huang, J., Chan, E. O.-T., Liu, X., Lok, V., Ngai, C. H., Zhang, L., Xu, W., Zheng, Z.-J., Chiu, P. K.-F., Vasdev, N., Enikeev, D., Shariat, S. F., Ng, C.-F., Teoh, J. Y.-C., & Wong, M. C. S. (2023). Global Trends of Prostate Cancer by Age, and Their Associations With Gross Domestic Product (GDP), Human Development Index (HDI), Smoking, and Alcohol Drinking. Clinical Genitourinary Cancer.
[29]	Kane, C. J., Lubeck, D. P., Knight, S. J., Spitalny, M., Downs, T. M., Grossfeld, G. D., Pasta, D. J., Mehta, S. S., & Carroll, P. R. (2003). Impact of patient educational level on treatment for patients with prostate cancer : Data from CaPSURE. Urology, 62(6), 1035‑1039.
[30]	Kilpeläinen, T. P., Talala, K., Taari, K., Raitanen, J., Kujala, P., Pylväläinen, J., Tammela, T. L., & Auvinen, A. (2020). Patients’ education level and treatment modality for prostate cancer in the Finnish Randomized Study of Screening for Prostate Cancer. European Journal of Cancer (Oxford, England: 1990), 130, 204‑210.
[31]	Liu, D., Kuai, Y., Zhu, R., Zhou, C., Tao, Y., Han, W., & Chen, Q. (2020). Prognosis of prostate cancer and bone metastasis pattern of patients : A SEER-based study and a local hospital based study from China. Scientific Reports, 10(1), Article 1.
[32]	Tyson, M. D., Andrews, P. E., Etzioni, D. A., Ferrigni, R. G., Humphreys, M. R., Swanson, S. K., & Castle, E. K. (2013). Marital status and prostate cancer outcomes. The Canadian Journal of Urology, 20(2), 6702‑6706.
[33]	Liu, Y., Xia, Q., Xia, J., Zhu, H., Jiang, H., Chen, X., Zheng, Y., Zhang, F., & Li, S. (2019). The impact of marriage on the overall survival of prostate cancer patients : A Surveillance, Epidemiology, and End Results (SEER) analysis. Canadian Urological Association Journal, 13(5), E135‑E139.
[34]	Guo, Z., Gu, C., Li, S., Gan, S., Li, Y., Xiang, S., Gong, L., & Wang, S. (2021). Association between Marital Status and Prognosis in Patients with Prostate Cancer : A Meta-Analysis of Observational Studies. Urology Journal, 18(04), Article 04.
[35]	Bray, F., Ferlay, J., Soerjomataram, I., Siegel, R. L., Torre, L. A., & Jemal, A. (2018). Global cancer statistics 2018 : GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA: A Cancer Journal for Clinicians, 68(6), 394‑424.
[36]	Chowdhury-Paulino, I. M., Ericsson, C., Vince Jr., R., Spratt, D. E., George, D. J., & Mucci, L. A. (2022). Racial disparities in prostate cancer among black men : Epidemiology and outcomes. Prostate Cancer and Prostatic Diseases, 25(3), Article 3.
[37]	Drozdz-Afelt, J. M., Koim-Puchowska, B., Klosowski, G., & Kaminski, P. (2020). Polymorphism of glutathione S-transferase in the population of Polish patients with carcinoma of the prostate. Environmental Science and Pollution Research, 27(16), 19375‑19382.
[38]	Liu, D., Che, B., Chen, P., He, J., Mu, Y., Chen, K., Zhang, W., Xu, S., & Tang, K. (2022c). GSTT1, an increased risk factor for prostate cancer in patients with metabolic syndrome. Journal of Clinical Laboratory Analysis, 36(4), e24352.
[39]	39. Reddy, P., Naidoo, R.N., Robins, T.G., MentzLi, G.H., London, S.J. and Batterman, S. (2012) GSTM1 and GSTP1 Gene Variants and the Effect of Air Pollutants on Lung Function Measures in South African Children. American Journal of Industrial Medicine, 55, 1078-1086.
[40]	Malik, S. S., Masood, N., & Yasmin, A. (2015). Prostate cancer and glutathione S-transferase deletions. EXCLI Journal; 14:Doc1049; ISSN 1611-2156.
[41]	Lopez-Bigas, N., & Gonzalez-Perez, A. (2020). Are carcinogens direct mutagens? Nature Genetics, 52(11), Article 11.