DNA repair XRCC1 Arg399Gln polymorphism alone, and in combination with CYP2E1 polymorphisms significantly contribute to the risk of development of childhood acute lymphoblastic leukemia

Tumer, Tugba Boyunegmez; Yilmaz, Duygu; Tanrikut, Cihan; Sahin, Gurses; Ulusoy, Gulen; Arinç, Emel

doi:10.1016/j.leukres.2010.02.035

« Previous Next »Leukemia Research
Volume 34, Issue 10 , Pages 1275-1281, October 2010

DNA repair XRCC1 Arg399Gln polymorphism alone, and in combination with CYP2E1 polymorphisms significantly contribute to the risk of development of childhood acute lymphoblastic leukemia

Tugba Boyunegmez Tumer
- Biochemistry Graduate Programme and Department of Biological Sciences, Middle East Technical University, 06531 Ankara, Turkey
- Vocational School of Health Services, Çanakkale Onsekiz Mart University, 17100, Çanakkale, Turkey
- Corresponding author. Current address: Vocational School of Health Services, Çanakkale Onsekiz Mart University, 17100 Çanakkale, Turkey. Tel.: +90 286 2171001; fax: +90 286 2128804.
Duygu Yilmaz
- Biochemistry Graduate Programme and Department of Biological Sciences, Middle East Technical University, 06531 Ankara, Turkey
Cihan Tanrikut
- Biochemistry Graduate Programme and Department of Biological Sciences, Middle East Technical University, 06531 Ankara, Turkey
Gurses Sahin
- Department of Oncology, Dr. Sami Ulus Children's Hospital, Ankara, Turkey
Gulen Ulusoy
- Biochemistry Graduate Programme and Department of Biological Sciences, Middle East Technical University, 06531 Ankara, Turkey
- Department of Chemistry, College of Sciences, Koç University, Istanbul, Turkey
Emel Arinç
- Biochemistry Graduate Programme and Department of Biological Sciences, Middle East Technical University, 06531 Ankara, Turkey

Received 15 October 2009; received in revised form 19 February 2010; accepted 27 February 2010. published online 07 March 2011.

Abstract

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.