and Rs156697 Polymorphism in Influence the Risk and Therapeutic Outcome of B-Acute Lymphoblastic Leukemia Patients

Overview

Journal Front Oncol

Specialty Oncology

Date 2021 Nov 1

PMID 34722260

Citations 2

Authors

Shahid M Baba

Arshad A Pandith

Zafar A Shah

Sajad A Geelani

Javid R Bhat

Ayaz Gul

Sameer A Guru

Hamed A El-Serehy

Abid M Koul

Sheikh Mansoor

Affiliations

Soon will be listed here.

Abstract

Introduction: Glutathione S-transferase (GST) gene deletion or polymorphic sequence variations lead to decreased enzyme activity that influences susceptibility and response to chemotherapy in acute lymphoblastic leukemia (ALL). This case-control study investigated the association of GST gene polymorphisms with the etiology and therapeutic outcome of B-ALL among Kashmiri population.

Methods: A total of 300 individuals including 150 newly diagnosed B-ALL patients and an equal number of age and gender matched controls were genotyped for five GST gene polymorphisms by polymerase chain reaction-restriction fragment length polymorphism technique (PCR-RFLP) and multiplex PCR techniques.

Results: Higher frequency of , AG, and GG genotypes was observed in ALL cases compared to controls that associated significantly with ALL risk ( OR = 2.93, = 0.0001; AG: OR = 2.58, = 0.01; -GG: OR = 3.13, = 0.01). , , and SNPs showed no significant association ( 0.05). Combined genotype analysis revealed significant association of / (OR = 4.11, = 0.011) and /-AG (OR = 4.93, = 0.0003) with B-ALL susceptibility. Haplotype analysis of rs4925 and rs156697 revealed that carriers of CG haplotype had increased risk of B-ALL ( = 0.04). Kaplan-Meier plots revealed significantly inferior 3-year disease-free survival for -GG carriers ( = 0.002). Multivariate analysis confirmed -GG as an independent poor prognostic factor for DFS (HR = 4.5, = 0.034). Among combined genotypes, only /-AG associated significantly with poorer DFS rates ( = 0.032).

Conclusion: This study demonstrated that individually or in combination with GSTM1 and -AG genotypes associated with increased B-ALL risk. Also, rs156697 variant genotypes (AG and GG) associated with B-ALL, whereas the GG genotype of rs156697 influenced the treatment outcome.

Citing Articles

Association Between the Individual and Combined Effects of the and Polymorphisms and Risk of Leukemia: A Meta-Analysis.

Hu T, Zhou G, Li W Front Genet. 2022; 13:898937.

PMID: 35938012 PMC: 9355274. DOI: 10.3389/fgene.2022.898937.

Increased Risk of Acute Lymphoblastic Leukemia in Adult Patients with GSTM1 Null Genetic Polymorphism.

Abdalhabib E, Alzahrani B, Alanazi F, Algarni A, Ibrahim I, Mohamed H Pharmgenomics Pers Med. 2022; 15:227-234.

PMID: 35313604 PMC: 8934168. DOI: 10.2147/PGPM.S356302.

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