Lack of association between functional polymorphism of DNA repair genes (XRCC1, XPD) and clinical response in Indian chronic myeloid leukemia patients

The resistance for the tyrosine kinase inhibitors in chronic myeloid leukemia (CML) occurs mainly due to BCR/ABL1 dependent and independent mechanisms. The defective DNA repair due to functional polymorphisms in DNA repair genes, might act as an etiological factor for leukemia progression. The study...

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Bibliographic Details
Published in:	Molecular biology reports Vol. 46; no. 5; pp. 4997 - 5003
Main Authors:	Dhangar, Somprakash, Shanbhag, Vinay, Shanmukhaiah, Chandrakala, Vundinti, Babu Rao
Format:	Journal Article
Language:	English
Published:	Dordrecht Springer Netherlands 01-10-2019 Springer Nature B.V
Subjects:	Adolescent Adult Aged Animal Anatomy Animal Biochemistry Antineoplastic Agents - administration & dosage Biomedical and Life Sciences Child Chronic myeloid leukemia Cytogenetics Deoxyribonucleic acid DNA DNA Repair DNA-Binding Proteins - genetics Drug Resistance, Neoplasm Female Gene polymorphism Genetic Association Studies Genetic Predisposition to Disease Genotyping Histology Humans Imatinib Imatinib Mesylate - administration & dosage Imatinib Mesylate - pharmacology India - epidemiology Leukemia Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics Leukemia, Myelogenous, Chronic, BCR-ABL Positive - metabolism Life Sciences Male Middle Aged Morphology Myeloid leukemia Original Article Patients Polymorphism, Genetic Protein-tyrosine kinase Single-nucleotide polymorphism Statistical analysis Targeted cancer therapy X-ray Repair Cross Complementing Protein 1 - genetics X-ray Repair Cross Complementing Protein 1 - metabolism Xeroderma Pigmentosum Group D Protein - genetics Xeroderma Pigmentosum Group D Protein - metabolism XPD protein XRCC1 protein India Chronic myeloid leukemia (CML) Single nucleotide polymorphisms (SNPs) Double strand break (DSB) DNA repair genes Clinical response Imatinib mesylate
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Summary:	The resistance for the tyrosine kinase inhibitors in chronic myeloid leukemia (CML) occurs mainly due to BCR/ABL1 dependent and independent mechanisms. The defective DNA repair due to functional polymorphisms in DNA repair genes, might act as an etiological factor for leukemia progression. The study was carried out to understand the role of DNA repair genes (XRCC1, XPD) polymorphisms in Imatinib mesylate (IM) resistant CML patients. The study was carried out in total 87 CML patients (43 nonresponders-cases and 44 responders) who were treated with Imatinib. The treatment and follow-up was done according to European LeukemiaNet guidelines. The genotyping of selected SNPs were studied using RFLP and confirmed with Sanger sequencing (20%). The statistical analysis was performed using online tools (Socscistatistics and GraphPad InStat software). In our study no significant association was inferred between genotypes of DNA repair genes (XRCC1; rs1799782, rs25487, and XPD ; rs13181) and complete cytogenetic response as well as molecular response. However there might be a possibility of association between XRCC1 Arg399Gln genotype AA/GA and cytogenetic response though it is statistically insignificant (p > 0.05). Though none of the genotypes of the DNA repair genes showed association with IM response, near association between XRCC1Arg399Gln genotype and cytogenetic response observed in our study. Hence, large sample size should be studied to establish the association of SNPs of DNA repair genes and IM response. Our study is a novel and important to explain the role of DNA repair genes polymorphisms in IM resistance.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0301-4851 1573-4978
DOI:	10.1007/s11033-019-04950-0