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Tumor Biology

, Volume 37, Issue 1, pp 791–798 | Cite as

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

Original Article

Abstract

There are a paucity and contradicted data about the impact of concurrent heredity of polymorphic genes and risk of chronic myeloid leukemia (CML). In the present study, the concurrent effects of three polymorphisms affecting the integrity of DNA consist of ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp on development of chronic myeloid leukemia were studied. Furthermore, the role of these polymorphisms in clinical and laboratory outcomes of patients was evaluated. In this case–control study, 70 CML patients and 140 healthy individuals were enrolled in the study. The clinical features of patients such as phase of disease and response to treatment and laboratory data before and after treatment with imatinib mesylate were collected. ABCB1 C3435T, ABCG2 C421A, and XRCC1 Arg194Trp single nucleotide polymorphisms were evaluated by restriction fragment length polymorphism–polymerase chain reaction. The T allele of ABCB1 C3435T, T allele of XRCC1 Arg194Trp, and C allele of ABCG2 C421A polymorphisms were significantly higher in patients than controls. TT genotype of ABCB1 and TT genotype of XRCC1 were associated with higher risk of chronic myeloid leukemia development. CC421 ABCG2/TT3435 ABCB1 and CC421 ABCG2/TT27157 XRCC1 were also correlated with a higher risk of CML. Patients with C allele of ABCB1 had poor cytogenetic response, and correlation of CC421 ABCG2/TT3435 ABCB1 diplotype with accelerated phase of CML was significant. Patients with CC421 ABCG2/TT3435 ABCB1 and CC421 ABCG2/TT27157 XRCC1 diplotypes might be at higher risk to rapid and severe development of CML and have weaker response to treatments with imatinib.

Keywords

ABCB1 ABCG2 Chronic myeloid leukemia Imatinib mesylate Polymorphism XRCC1 

Notes

Acknowledgments

The authors wish to thank all patients and health stuffs who participated in this study. This work has no financial support.

Conflicts of interest

None

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2015

Authors and Affiliations

  1. 1.Department of Biology, Sanandaj BranchIslamic Azad UniversitySanandajIran
  2. 2.Cellular and Molecular Research Center, Faculty of MedicineKurdistan University of Medical SciencesSanandajIran
  3. 3.Department of Clinical Biochemistry, Faculty of MedicineKurdistan University of Medical SciencesSanandajIran
  4. 4.Department of Internal Medicine, Faculty of MedicineKurdistan University of Medical SciencesSanandajIran
  5. 5.Liver and Digestive Research CenterKurdistan University of Medical SciencesSanandajIran
  6. 6.Department of Epidemiology and Biostatistics, Faculty of MedicineKurdistan University of Medical SciencesSanandajIran
  7. 7.Division of Hematology–OncologyTohid HospitalSanandajIran

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