Polymorphisms of xeroderma pigmentosum genes (XPC, XPD, and XPG) and susceptibility to acute leukemia among a sample of Egyptian patients

Abstract

DNA repair systems play a key role in protecting the DNA from damage caused by different endogenous and environmental factors. Genetic polymorphisms in DNA repair genes may lead to increased cancer susceptibility including leukemia. Due to different environmental genetic interactions among each population, the aim of the current study was to assess the association between three genetic polymorphisms of xeroderma pigmentosum complementation group: XPD (rs13181), XPC (rs2228001), and XPG (rs17655) and the susceptibility to acute leukemia in Egypt. The present study included 50 patients with acute leukemia, in addition to 100 normal volunteers as control group. Genotyping for the genes was done by PCR-RFLP technique. The study revealed that patients homovariant for XPD had fourfold increased risk of developing AML (OR = 4.4, P = 0.025) either alone or with variant genotypes of XPC and XPG. No statistically significant association was found between neither individual nor combined polymorphisms and disease risk of ALL in this study. Determination of XPD polymorphism could be considered as molecular markers associated with susceptibility to develop AML.

The Role of DNA Repair (XPC, XPD, XPF, and XPG) Gene Polymorphisms in the Development of Myeloproliferative Neoplasms

“…In the present study, variant genotypes of XPG 3507G>C were not associated with the risk of developing MPN. Our findings are consistent with those reported by ElMahgoub following a study of 50 Egyptian patients with acute leukemia [ 13 ]. As a similarity, Ruiz-Cosano et al, following a study of 213 cases and 214 controls, reported that XPG 3507G>C polymorphism was not associated with the risk of lymphoma (OR = 1.1; 95% CI = 0.8–1.7) [ 66 ].…”

“…Blood samples were used for genomic DNA extraction performed with the Quick-gDNA MiniPrep kits (Zymo Research, Irvine, CA, USA) and PureLink Genomic DNA Mini kits (Invitrogen, Carlsbad, CA, USA). The polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP) method was used in establishing the genotypes of XPC 1496C>T, XPC 2920A>C, XPD 2251A>C, XPF -673C>T, XPF 11985A>G, and XPG 3507G>C, as previously described [ 13 , 27 , 37 , 46 , 47 , 48 ]. After the PCR reaction, digestion was performed with specific restriction enzymes (Thermo Fisher Scientific, Waltham, MA, USA), followed by agarose gel electrophoresis (2%) ( Table 3 ).…”

“…One of the most important DNA pathways is represented by nucleotide excision DNA repair (NER). NER is capable of identifying the DNA damage and removing the chemically and structurally different helix-distorting DNA lesions [ 13 , 14 ]. Seven proteins are considered the main participants of NER and make up the Xeroderma pigmentosum complementary group [ 15 ].…”

B- Acute Lymphoblastic Leukaemia in A Boy With Xeroderma Pigmentosum

“…In a study by ElMahgoub IR et.al, which evaluated polymorphisms of xeroderma pigmentosum genes (XPC, XPD, and XPG) and susceptibility to acute leukaemia among a sample of Egyptian patients, homovariant for XPD had four fold increased risk of developing AML (OR = 4.4, P = 0.025) either alone or with variant genotypes of XPC and XPG. 6 The published cases of XP with haematological malignancies are summarised in table 1. Most of the patients were adolescents, with the youngest being a 7 year old with B-ALL with MDS.…”

Sportive activity reduces genomic damage

“…Xeroderma Pigmentosum group C) gene belongs to the Nucleotide Excision Repair (NER) pathway; this gene encodes a protein binding damaged DNA in apoptosis and in the rst phases of DNA repair [27]. The Lys939Gln polymorphism of this gene consists in an A > C transition at codon 939 of exon 15; this polymorphism has been studied in relation to the probability of developing many cancer types, with inconsistent results [27,28,29].…”