XRCC1 polymorphisms and haplotypes in Mexican patients with acute lymphoblastic leukemia

Abstract

We examined the influence of the Arg194Trp, Arg280His, and Arg399Gln polymorphisms of XRCC1 (X-ray repair cross-complementing group 1) on the development of childhood acute lymphoblastic leukemia (ALL) in 120 ALL patients and 120 controls in Mexico. All of them were genotyped for these polymorphisms, using polymerase chain reaction. No significant differences in allele and genotype frequencies for any polymorphism were observed between patients and controls. Estimation of haplotypes showed the eight expected haplotypes (A-H), seven of which were found in both patients and controls; haplotype A (Arg-Arg-Arg) was the most common, whereas haplotypes F and G were absent in patients and controls, respectively. Haplotype B (Trp-Arg-Arg) was found to be associated with an increased risk of ALL (odds ratio (OR) = 1.95, 95% confidence interval (CI) = 1.13-3.37; P = 0.016), particularly in males (OR = 2.65, 95%CI = 1.25-5.63; P = 0.01). Individually, the 194Trp, 280His, and 399Gln alleles were not associated with significantly increased risk for ALL in these Mexican children.

Concurrent effects of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp genetic polymorphisms with risk of cancer, clinical output, and response to treatment with imatinib mesylate in patients with chronic myeloid leukemia

“…Finally, it has been revealed that XRCC1 Arg194Trp SNP (rs1799782) is a functional polymorphism and could affect the XRCC1 role, decrease the kinetics of repair mechanism, and influence susceptibility to cancer [25,26]. The role of XRCC1 polymorphisms in susceptibility to acute myeloid leukemia (AML) [27][28][29], acute lymphoblastic leukemia [30], chronic lymphocytic leukemia [31], and lymphoma [32] have been widely studied.…”

Epidemiology and Polymorphisms Related to Bladder Cancer in Ecuadorian Individuals

“…Some reports in human populations suggested the 399Gln variant of XRCC1 was associated with greater DNA and chromosomal damage (Yoon, et al, 2011). It has been suggested that changes in the XRCC1 protein, mainly in amino acid 399, increase the susceptibility for tumor development via genomic instability (Meza-Espinoza, et al, 2009). Nevertheless, another study did not find any effect of the Arg399Gln polymorphisms with regard to DNA damage (Pastorelli et al, 2002), even though it is not well known whether these polymorphisms produce a functional change in the protein.…”

DNA Repair Deficiency Associated with Hematological Neoplasms

“…Similarly, polymorphism XRCC1 Arg194Trp, has been found to have a protective effect in Thais (Pakakasama et al 2007), while opposite results have been found in another study (Joseph et al 2005). Moreover, several XRRC1 haplotypes have been related to ALL; haplotype B, as well as C, have been associated with an increased ALL risk (Meza-Espinoza et al 2009, Pakakasama et al 2007). On the other hand, polymorphisms of Nucleotide Excision Repair genes have also been investigated in ALL in a few studies.…”

“…Several polymorphisms have been implicated, but results are somewhat conflicting, probably because of the different ethnic groups involved in each study. Thus, polymorphism XRCC1 Arg399Gln has been associated with increased risk of childhood ALL, in Indians (Joseph et al 2005), Chinese (Zhu et al 2005) and Thais (Pakakasama et al 2007), but no correlation was found in Mexican (Meza-Espinoza et al 2009), Brazilian (da Silva Silveira et al 2009) and Turkish children (Batar et al 2009). Perhaps this polymorphism has a stronger effect or a higher penetrance in Asian populations.…”