Pharmacogenomics and Personalized Medicine (Mar 2022)
Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism
Abstract
Ezeldine K Abdalhabib,1 Badr Alzahrani,1 Fehaid Alanazi,1 Abdulrahman Algarni,2 Ibrahim Khider Ibrahim,3 Hozifa A Mohamed,4,5 Hassan A Hamali,6 Abdullah A Mobarki,6 Gasim Dobie,6 Muhammad Saboor6,7 1Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Jouf University, Al-Qurayyat, Saudi Arabia; 2Department of Medical Laboratory Technology, College of Applied Medical Sciences, Northern Borders University, Arar, Saudi Arabia; 3Department of Hematology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 4Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Al Neelain University, Khartoum, Sudan; 5Department of Molecular Biology, Faculty of Medical Laboratory Sciences, Sudan International University, Khartoum, Sudan; 6Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, Jazan University, Jazan, Saudi Arabia; 7Medical Research Center (MRC), Jazan University, Jazan, Saudi ArabiaCorrespondence: Muhammad Saboor, Department of Medical Laboratory Technology, Faculty of Applied Medical Science, Jazan University, Jazan, Saudi Arabia, Tel +966 54 495 9029, Email [email protected]: Glutathione S-transferases (GSTT1 and GSTM1) detoxify various endogenous and exogenous compounds and provide cytoprotective role against reactive species. This study aimed to assess the frequency of GSTT1, and GSTM1 polymorphisms in newly diagnosed Sudanese adult patients with acute lymphoblastic leukemia (ALL) and to evaluate the association of these polymorphisms with age, gender and type of ALL.Patients and Methods: This case–control study included 128 adult Sudanese, untreated newly diagnosed patients with ALL, aged 18 to 74 years and 128 age-gender matched healthy controls. Deletional polymorphisms of GSTT1 and GSTM1 genes were genotyped through a multiplex polymerase chain reaction (PCR) assay using β-globin gene as an internal positive control.Results: The genotypic frequency of GSTT1 null polymorphism was 22.7% in cases and 14.8% in controls (OR = 1.68, P = 0.111). Statistically significant differences were noted in the frequencies of GSTM1 null polymorphism in cases and controls (OR = 3.7, P = < 0.001). Combined GSTT1 null and GSTM1 null gene polymorphisms showed statistically significant difference in patients with ALL as compared to controls (OR = 6.5, CI 95% = 1.42– 29.74, P < 0.001).Conclusion: Irrespective of age at diagnosis, gender, and phenotype of ALL, GSTM1 null polymorphism either alone or in combination with GSTT1 null polymorphism poses significantly increased risk of developing ALL in adults.Keywords: GSTT1, GSTM1, polymorphism, acute lymphoblastic leukemia