DNA repair XRCC1 Arg399Gln polymorphism alone, and in combination with CYP2E1 polymorphisms significantly contribute to the risk of development of childhood acute lymphoblastic leukemia
| Autor: | Cihan Tanrikut, Duygu Vefikuluçay Yilmaz, Gulen Ulusoy, Emel Arinç, Tugba Boyunegmez Tumer, Gürses Şahin |
|---|---|
| Rok vydání: | 2010 |
| Předmět: |
Male
Risk Oncology Cancer Research medicine.medical_specialty Turkish population Adolescent DNA Repair Single-nucleotide polymorphism Biology XRCC1 Internal medicine Genotype medicine Humans Allele Child Childhood Acute Lymphoblastic Leukemia Genetics Polymorphism Genetic Haplotype Infant Cytochrome P-450 CYP2E1 Hematology Precursor Cell Lymphoblastic Leukemia-Lymphoma DNA-Binding Proteins X-ray Repair Cross Complementing Protein 1 Child Preschool Female Risk assessment DNA Damage |
| Zdroj: | Leukemia Research. 34:1275-1281 |
| ISSN: | 0145-2126 |
| Popis: | It is now well established that genetic polymorphisms impairing the DNA repair capacity can disrupt the genomic integrity and potentially modulate individual's susceptibility to various cancers. In this study, we investigated the possible association of X-ray repair cross-complimenting group 1 (XRCC1) Arg399Gln and Arg194Trp variants with the risk of incidence of childhood acute lymphoblastic leukemia (ALL) in Turkish population comprised of 190 healthy controls and 167 ALL patients. For Arg399Gln polymorphism, the heterozygous (Arg/Gln) and homozygous mutant (Gln/Gln) genotypes were significantly more common in the ALL patients than the controls (OR: 1.6, p = 0.04). Particularly, the Gln399Gln genotype significantly increased the risk of disease up to 2.0-fold (OR: 2.0, p = 0.04). Besides, Gln399Gln genotype has been found to be associated with considerably increased risk of ALL among females (OR = 2.9, p = 0.03). In case of codon 194 polymorphism, no significant associations have been found with risk of childhood ALL. In addition, none of the combinations of XRCC1 codon 194 and 399 polymorphisms have been found to be significantly associated with childhood ALL risk. In the scope of this study, we have also showed that the co-presence of XRCC1 codon 399 and CYP2E1*5B and *6 polymorphisms (data for CYP2E1 polymorphisms drawn from previously published study conducted in our lab) in the same individuals considerably increased the risk for childhood ALL to 3.7-fold with borderline significance ( p = 0.049). The observed combined effect was considerably more prominent among females (OR = 17.4, p = 0.001) and need to further investigation. This is the first study showing combined associations of XRCC1 399Gln, CYP2E1*5B and *6 alleles with the risk of development of childhood ALL. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect