Multidrug resistance gene 1 C1236T polymorphism and susceptibility to leukemia: A meta-analysis

Abstract

Abstract. Several studies have investigated the association between multidrug resistance gene (MDR1) C1236T polymorphism and leukemia risk, however, these published studies have yielded conflicting results. Thus, the present study carried out a meta-analysis to provide a more precise estimate of the effect of this polymorphism on the susceptibility to leukemia. The published case-control studies regarding the association between MDR1 C1236T polymorphism and leukemia risk were included following a computerized search of PubMed, Elsevier, The Cochrane Library, China National Knowledge Infrastructure and Wanfang Database. Either fixed-or random-effects models were applied to calculate the combined odds ratios (ORs) and 95% confidence intervals (CIs) by RevMan 5.2 software. Seven studies, including 846 cases and 1,523 controls, were included in the present meta-analysis. The results indicated that there was no significant association between the MDR1 C1236T polymorphism and leukemia risk in overall comparisons in all four genetic models (CT vs. CC: OR, 1.31, 95% CI, 0.89-1.91, P= 0.17; TT vs. CC: OR, 2.16, 95% CI, 0.99-4.70, P= 0.05; TT vs. CC+CT: OR, 1.72, 95% CI, 0.91-3.25, P= 0.09; and CT+TT vs. CC: OR, 1.57, 95% CI, 0.96-2.56, P= 0.07). In the subgroup analysis according to specific ethnicity, age and the type of leukemia, a significant association was found in adult leukemia (CT+TT vs. CC: OR, 2.77, 95% CI, 1.05-7.31, P=0.04) and chronic myeloid leukemia (CT vs. CC: OR, 1.71, 95% CI, 1.05-2.80, P=0.03). No significant publication bias was detected by funnel plot. Therefore, the meta-analysis indicated that the MDR1 C1236T polymorphism may contribute to the susceptibility to adult leukemia and chronic myeloid leukemia. Furthe well-designed studies based on larger sample sizes are required to validate these findings. IntroductionLeukemia is a malignant clonal disorder of the hematopoietic system with extreme heterogeneity and bad prognosis. In recent years, the incidence of leukemia increased gradually (1), however, the exact biological mechanisms of leukemia have not been fully clarified (2). Epidemiological and case-control studies have found that significant environmental exposures contribute to the pathogenesis of leukemia (3). In addition, previous candidate gene association approaches and genome-wide association studies have identified the presence of inherited genetic susceptibility to this disease (4-7). Therefore, it is generally considered that the causation is multifactorial and that the interaction between exogenous or endogenous exposures and genetic susceptibility plays an important role in the etiology of leukemia (2).The human multidrug resistance gene (MDR1 or ABCB1) locates at 7q21.1 and its cDNA spans ~4.5 kb. MDR1 encodes a 170-kDa membrane transport protein called P-glycoprotein (P-gp), belonging to the adenosine triphosphate (ATP)-binding cassette (ABC) superfamily of transporters (8). P-gp functions as an ATP-dependent efflux pump and is responsible for the efflux of a variety of lipophilic...

Multidrug resistance 1 (MDR1/ABCB1) gene polymorphism (rs1045642 C > T) and susceptibility to multiple myeloma: a systematic review and meta-analysis

“…Since P-glycoprotein acts as an efflux pump that protects cells against endogenous and exogenous harmful compounds, especially environmental carcinogens, any MDR 1 SNP might alter the P-glycoprotein expression and protein conformation that subsequently culminated in the development of several cancer types including hematologic malignancy as a result of carcinogens' accumulation in cells [31,32]. Among three common SNPs in MDR 1 , including 3435C > T, 1236C > T, and 2677G > T/A, unlike the 2677G > T/A polymorphism which is a non-synonymous SNP and causes an amino acid substitution, the 3435C > T and 1236C > T polymorphisms are synonymous SNPs, not causing a change in the amino acid.…”

MDR1 polymorphisms have an impact on the prognosis of Chinese diffuse large B cell lymphoma patients

“…Some single nucleotide polymorphism (SNP) studies in MDR1 gene have indicated their effect on gene expression and/or protein function, which might be associated with development of cancers, chemotherapy response, and clinical prognosis in tumor patients [8][9][10]. Among the discovered SNPs, C1236T (Exon 12, rs1128503), C3435T (Exon 26, rs1045642), and G2677T/A (Exon 21, rs2032582) are the most common and mainly focused on polymorphisms in the coding region of MDR1 [11][12][13]. Several studies confirmed these three SNPs might have a major impact on the genetic susceptibility to hematopoietic malignancies, as well as the prognosis [13][14][15].…”

Genetic Polymorphisms Associated to Folate Transport as Predictors of Increased Risk for Acute Lymphoblastic Leukemia in Mexican Children

“…The scientific literature, as reported by Ma et al ( 2015a , b ) in two meta-analysis indicate no clear association between this polymorphism and risk to ALL. In our study, we found that the rs1045642 ABCB1 SNP (known as 3435C > T) was associated with a risk of ALL occurrence.…”