title: 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.
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.
authors.affiliation: Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.
authors.forename: Hana
authors.initials: H
authors.lastname: Salimizand
authors.affiliation: Department of Biology, Sanandaj Branch, Islamic Azad University, Sanandaj, Iran.
authors.forename: Sabrieh
authors.initials: S
authors.lastname: Amini
authors.affiliation: Cellular and Molecular Research Center, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. abdi@muk.ac.ir.|Department of Clinical Biochemistry, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. abdi@muk.ac.ir.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Abdi
authors.affiliation: Department of Internal Medicine, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran. bayazidg@yahoo.com.|Liver and Digestive Research Center, Kurdistan University of Medical Sciences, Sanandaj, Iran. bayazidg@yahoo.com.|Division of Hematology-Oncology, Tohid Hospital, Geryashan Boulevard, Sanandaj, Iran. bayazidg@yahoo.com.
authors.forename: Bayazid
authors.initials: B
authors.lastname: Ghaderi
authors.affiliation: Department of Epidemiology and Biostatistics, Faculty of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
authors.forename: Namam-Ali
authors.initials: NA
authors.lastname: Azadi
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics / Q000378:metabolism; D000328:Adult; D016022:Case-Control Studies; D003582:Cytogenetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005260:Female; D015973:Gene Expression Regulation, Leukemic; D005838:Genotype; D006801:Humans; D000068877:Imatinib Mesylate / Q000008:administration & dosage*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D015995:Prevalence; D016896:Treatment Outcome; D000076105:X-ray Repair Cross Complementing Protein 1
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D004268:DNA-Binding Proteins; D000076105:X-ray Repair Cross Complementing Protein 1; C000619371:XRCC1 protein, human; D000068877:Imatinib Mesylate
keywords: ABCB1; ABCG2; Chronic myeloid leukemia; Imatinib mesylate; Polymorphism; XRCC1