Genotype Analysis of ABCC1, NCF4 and CBR3 Polymorphism and the Association With Childhood Acute Lymphoblastic Leukemia in Mexican Childhood Population

Abstract

Background: The identification of genetic risk factors for Acute Lymphoblastic Leukemia (ALL), are increasingly urgent and necessary.Objective: The purpose of this study is to determine the association of the genetic polymorphisms ABCC1 rs3743527, NCF4 rs1883112 and CBR3 rs1056892 with ALL.Methods: DNA samples were obtained in 71 children with ALL (from 2 to 18 years) and in 71 controls without ALL, to determine the polymorphisms by real-time polymerase chain reaction (qPCR), using specific TaqMan probes in a StepOne® thermal cycler (Applied Biosystems, United States).Results: The results of the Odds Ratio analysis show that in the rs1883112 polymorphism of the NCF4 gene, the heterozygous allele has a risk effect for ALL (OR = 3.1870, CI = 1.8880–7.9383 and p = 0.0002), in turn the mutated genotype (AA) is associated with a protective effect (OR = 0.26, 0.1248 to 0.5434 and p = 0.0003). On the other hand, the CBR3 rs1056892 polymorphism shows a significant association of risk to ALL, in the presence of the HT genotype (OR = 2.77, IC = 1.3837 to 5.5651 and p = 0.004) and the mutated genotype of this polymorphism has a significant association with protection to ALL in the HM genotype (OR = 0.52, IC = 0.2639 to 1.0304 and p = 0.05). While the inheritance models of the polymorphisms let us see that of the rs1883112 polymorphism of the NCF4 polymorphism; the HT genotype of the codominant model shows a protective effect against ALL (OR = 0.4117, IC = 0.1718 to 0.9866 and p = 0.04), the recessive model shows us and confirms what we already saw in table number 3, being that there is an association with protective effect in the HM genotype (OR = 0.2604, IC = 0.1248 to 0.5434 and p = 0.0003). In the polymorphism rs1056892 of the CBR3 gene, a protection association was found in the heterozygous allele of the codominant model (OR = 0.3448, IC = 0.1375 to 0.8896 and p = 0.0274). In addition, the recessive inheritance model for the HM genotype shows a protective effect to ALL, (OR = 0.52, CI = 0.9919 to 3.8638 and p = 0.05).Conclusion: There is an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms with an increased risk of susceptibility to ALL; Likewise, through the codominant inheritance model, the effect of the variation of the CBR3 rs1056892 gene as a protective factor against ALL was evaluated.

Replication of genetic associations of chemotherapy-related cardiotoxicity in the adjuvant NSABP B-31 clinical trial

“…Among the more common variants, CBR3 rs1056892 showed a trend for association in the NSABP B-31 patients, p = 0.067 ( Table 1B ), in the same direction as in other published studies ( 9 , 11 , 16 – 18 ). LINC01060 rs7698718 was significantly more frequent in NSABP B-31 patients who experienced a cardiac event, cases allele A = 0.36, controls allele A = 0.21, p = 0.044 ( Table 1B ).…”

“…Secondly, we observed the association of CBR3 (Carbonyl-reductase 3) V244M, a polymorphism that has previously been associated with anthracycline-induced heart failure in childhood cancer patients ( 9 , 16 , 17 ) and in patients with breast cancer ( 7 , 10 , 11 , 18 ). The major allele variant, V244 (allele G), is associated with cardiotoxicity, and in biochemical assays, the same allele metabolizes doxorubicin 2.6 times faster than M244 (allele A) ( 9 , 26 ), and in line with these existing studies, in the NSABP B-31 patients, V244 (allele G) was more frequent in patients experiencing a cardiac event.…”

Genes of Predisposition to Childhood Beta-Cell Acute Lymphoblastic Leukemia in the Kazakh Population

“…Significant differences were found in a higher population frequency of the minor A allele in the South Asians -53.2% (p<0.001). It has been shown that CBR3 rs1056892 is significantly associated with a 3-fold risk of B-cell ALL with homozygous genotype G/G (OR = 2.77, 95% Cl: 1.384-5.565 and p = 0.004), the normal homozygous genotype A/A has considerable protective association with B-cell ALL (OR = 0.52, 95% Cl: 0.264-1.030 and p = 0.05) (Gándara-Mireles et al, 2021). Most of the conducted GWAS have found that the G/G rs1056892 correlates with a 3.3-fold increased risk of cardiomyopathy after anthracycline therapy compared with G/A, A/A genotypes (Lang et al, 2021).…”