Certain glutathione S-transferase (GST) polymorphisms are associated with an increased risk of B-cell acute lymphocytic leukemia (B-ALL), according to research published in Frontiers in Oncology.
ALL susceptibility appears to be influenced by many environmental and genetic components. Although treatment advances have led to great improvements in survival, about 20% of patients do not respond to treatment or have high toxicity.
The study authors evaluated 5 GST gene polymorphisms and their relation to the risk of developing B-ALL and influence on treatment outcome for patients in Kashmir. The study included 150 patients with B-ALL, with a median age of 16 years. These patients were compared to 150 matched controls without B-ALL.
A total of 40% of patients with B-ALL had GSTT1null genotype compared with 16% in the controls, which correlated with an increased risk of the disease (odds ratio [OR], 2.93; P =.0001). GSTM1null was not significantly associated with an increased risk.
GSTP polymorphisms were also not significantly associated with a higher risk for B-ALL. GSTO2 single nucleotide polymorphism (SNPs) AG and GG genotypes were associated with a higher risk for B-ALL.
The authors also evaluated survival with a median follow-up time of 19.2 months. A total of 82% of patients (n=123) achieved remission, 14% (n=21) relapsed, and 4% (n=6) died during the study. Overall survival (OS) was not associated with any GST SNPs.
However, GSTO2-GG was significantly associated with a worse 3-year probability of disease-free survival (DFS; 23% for GSTO2-GG vs 78.2% for GSTO2-AA and 93.7% for GSTO2-AG; P=.002).
GSTT1null/GSTP1-AG also had an inferior DFS of 42.7% compared to 81.3% for GSTT1present/ GSTP1-AA carriers (P=.037).
These results were consistent with the risks and outcomes found in other studies of B-ALL, but further studies are warranted with larger sample sizes and various ethnicities.
Baba SM, Pandith AA, Shah ZA, et al. GSTT1null and rs156697 polymorphism in GSTO2 influence the risk and therapeutic outcome of B-acute lymphoblastic leukemia patients. Front Oncol. 2021;11:714421. doi:10.3389/fonc.2021.714421