The Effect of B-Cell Lymphoma 2 and BCL2-Associated X  Polymorphisms on the Survival of Acute Lymphoblastic  Leukemia Patients: Application of Frailty Survival Models

Navideh  Nikmohammadi; Parvin  Sarbakhsh; Mozghan  Moazami Goudarzi; Mehdi Talebi; Majid  Farshdousti-Hagh; Jamileh  Malakouti; Neda  Gilani

doi:10.18502/ijph.v51i4.9251

Navideh Nikmohammadi Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
Parvin Sarbakhsh Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran
Mozghan Moazami Goudarzi Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Mehdi Talebi Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
Majid Farshdousti-Hagh Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
Jamileh Malakouti Department of Midwifery, Faculty of Nursing and Midwifery, Tabriz University of Medical Sciences, Tabriz, Iran
Neda Gilani Department of Statistics and Epidemiology, Faculty of Health, Tabriz University of Medical Sciences, Tabriz, Iran

DOI: https://doi.org/10.18502/ijph.v51i4.9251

Keywords: Acute lymphoblastic leukemia; B-Cell Lymphoma 2; BCL2-Associated X; Frailty models; Survival

Abstract

Background: B-cell lymphoma 2 (BCL-2) and BCL-2 associated X (BAX) polymorphisms are important in the apoptosis process, response to treatment and survival in Acute Lymphoblastic Leukemia (ALL) patients. We aimed to investigate the effect of these genes with other predictors corresponding to the survival of ALL patients with an appropriate frailty survival model.

Methods: Our study was performed in 2020 on sixty-two cases of childhood aged 3-16 (year) with ALL disease who were selected by convenience sampling from the two hospitals of Tabriz, Iran. RFLPPCR method was used for genotyping the promoter region of the BAX and BCL-2 genes. We used different frailty survival models, to control heterogeneity between individuals due to unmeasured factors affecting their survival. All analyses were implemented using Stata 16.

Results: Based on the result of log-logistic model along with frailty gamma, the proportional odds (standard error) of survival for a CC allele of BCL-2 patient compared to a AA allele patient were 6.0 (1.47); P<0.001 and for a AC of BCL-2 allele patient were 0.57 (1.23); P=0.009. Patients with AG allele of BAX had 2.05 (1.26) times greater odds of surviving than a AA allele patient (P=0.003). The odds of survival of patients with abnormal white blood cell (WBC) were 92% less than normal WBC (P<0.001).

Conclusion: With controlling unmeasured factors affecting, the BCL-2 and BAX genes promoter polymorphism are effective in the survival rates for ALL.