Is the MDR1 C3435T Polymorphism Responsible for Oral Mucositis in Children with Acute Lymphoblastic Leukemia?

Abstract

Background and Aim: Although the functional consequences of MDR-1 polymorphisms have been the subject of numerous studies, to the best to our knowledge, associations with clinical side effects of anticancer drugs have yet to be assessed. Our aim was to clarify any role of the C3435T polymorphism of the MDR1 gene in oral mucositis and its relation with elevated reactive oxygen species (ROS) levels, in children with acute lymphoblastic leukemia (ALL). Materials and Methods: The distribution of the MDR-1 C3435T polymorphism in 47 patients with ALL was determined by RFLP and compared with that of 68 healthy controls. Results: There were no association in distribution of genotypes of MDR-1 C3435T polymorphism and the risk of ALL. Oral mucositis were detected in 78.7% (n=37) of the patients and significantly related to the MDR-1 CT genotype (p=0.042), as confirmed by logistic regression analysis. Conclusion: Our preliminary data suggest that children carrying the CT genotype are more prone to develop oral mucositis, which might mean that the heterozygous genotype leads to accumulation of more reactive oxygen species. Since a limited number of patients was investigated, further studies are needed to confirm these findings.

ABCB1 C3435T polymorphism is associated with leukemia susceptibility: evidence from a meta-analysis

“…All the cases had a confirmed diagnosis of leukemia and the controls were mainly matched for age and sex. Among the included studies, six studies were conducted in an Asian population, 25 , 28 , 31 , 34 , 36 , 38 nine studies in a Caucasian population, 22 – 24 , 26 , 29 , 30 , 32 , 33 , 35 and two studies in a mixed population. 27 , 37 The distribution of genotypes among the control groups in four studies was not in agreement with HWE.…”

“… 27 , 37 The distribution of genotypes among the control groups in four studies was not in agreement with HWE. 22 , 33 , 35 , 36 …”

Association of MDR1 C3435T and C1236T single nucleotide polymorphisms with male factor infertility

“…According to our result, we also suggested that the CT genotype might be a susceptibility factor for infertility. Bektaş-Kayhan et al (2012) also described that children with acute lymphoblastic leukemia carrying the CT genotype are more prone to develop oral mucositis and might therefore also be more susceptible to the side effects of chemotherapy.…”

Lack of Association between Polymorphisms in Genes MTHFR and MDR1 with Risk of Childhood Acute Lymphoblastic Leukemia

“…Some studies suggest that functional polymorphisms in gene MDR1 might influence the course of the disease, as it has been reported that children carrying the CT (C3435T) genotype are more prone to develop oral mucosistis (Bektas-Kayhan et al, 2012).…”