Just Accepted by Leukemia & Lymphoma
Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tunisian population K Douzi, S Ouerhani, S Menif, Ines Safra, S Abbes Doi: 10.3109/10428194.2014.974045
Leuk Lymphoma Downloaded from informahealthcare.com by Dalhousie University on 11/13/14 For personal use only.
Abstract Human DNA repair mechanisms protect the genome from DNA damage caused by endogenous and environmental agents. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely reported in different cancers. In this study we aimed to evaluate the associations between XPCLys939Gln (rs2228001), XPD Lys 751Gln (rs13181) and XPG Asp1104His (rs17655) polymorphisms and leukemia risk in the Tunisian population. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP) in 206 leukemia patients and 206 healthy controls. We found an increased risk of leukemia among subjects carrying the XPC 939Gln/Gln genotype (OR=2.48, 95%CI=1.353 – 4.560, P=0.0042). Moreover, in subgroup analysis according to clinical types, CML patients showed a higher risk than AML and ALL patients (OR=3.87, 95%CI=1.820 – 8.237, P=0.0003). However, the XPD 751Gln allele may be protective against CML and AML development and no significant differences in genotypes frequencies were observed for XPG gene between patients and controls. Further studies with larger samples and risk factors information are needed.
© 2014 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tunisian population.
K Douzi, S Ouerhani, S Menif, Ines Safra, S Abbes
Correspondence: K Douzi, Laboratory of Molecular Hematology, Pasteur Institute, P.O. Box 74, Place Pasteur, Belvedere, 1002 Tunis, Tunisia. Phone number (+216) 71 78 30 22, Fax +216 71 79 18 33. Email: [email protected] Abstract
ST
AC
CE
Human DNA repair mechanisms protect the genome from DNA damage caused by endogenous and environmental agents. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely reported in different cancers. In this study we aimed to evaluate the associations between XPCLys939Gln (rs2228001), XPD Lys 751Gln (rs13181) and XPG Asp1104His (rs17655) polymorphisms and leukemia risk in the Tunisian population. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in 206 leukemia patients and 206 healthy controls. We found an increased risk of leukemia among subjects carrying the XPC 939Gln/Gln genotype (OR=2.48, 95%CI=1.353 – 4.560, P=0.0042). Moreover, in subgroup analysis according to clinical types, CML patients showed a higher risk than AML and ALL patients (OR=3.87, 95%CI=1.820 – 8.237, P=0.0003). However, the XPD 751Gln allele may be protective against CML and AML development and no significant differences in genotypes frequencies were observed for XPG gene between patients and controls. Further studies with larger samples and risk factors information are needed.
Keywords: Polymorphisms; DNA repair gene; CML, AML; ALL; XPC; XPD; XPG.
JU
Leuk Lymphoma Downloaded from informahealthcare.com by Dalhousie University on 11/13/14 For personal use only.
of Tunis El Manar, Tunis, Tunisia
PT ED
Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University
1. Introduction Leukemia is a heterogeneous group of hematological malignancies; in which hematopoietic progenitor cells acquire genetic lesions that lead to a block in differentiation, increased self-renewal and unregulated proliferation. Leukemia can be either acute or chronic and they can arise from myeloid or lymphoid cell lines or both in the case of myeloid/lymphoid or mixed lineage leukemia (MLL) [1 – 4].
PT ED
Leukemia can occur at any age, however chronic leukemias are usually found in persons over 40 years of age, whereas acute leukemias are generally found in
Although mutations have long been identified as early events in carcinogenesis [7] defective DNA repair is also a risk factor for many types of cancer [8 – 10]. Unrepaired DNA damage can either result in apoptosis or DNA aberrations leading
CE
to unregulated cell growth and cancer. In order to maintain genome integrity, damage caused to DNA by various agents must be repaired and preserved throughout the life of a cell. Among DNA repair mechanisms, the Nucleotide
AC
Excision DNA Repair (NER) is one of the major DNA repair pathway, and by which bulky adducts and wide variety of deleterious DNA lesions are removed from the genome [11, 12]. NER systems recognize the DNA damage, incise the DNA strand on both sides of the lesions, remove the oligonucleotide carrying the damage and
ST
re-synthetesis the fragment [13]. Genetic polymorphisms have been described for multiple genes associated with DNA repair and may modulate gene function and alter DNA repair capacity [14, 15]. An inability to respond adequately to DNA damage or failure to repair DNA damage
JU
Leuk Lymphoma Downloaded from informahealthcare.com by Dalhousie University on 11/13/14 For personal use only.
persons less than 20 years of age [5, 6].
accurately leads to genetic instability and to an increased cancer susceptibility including leukemia [16, 17].
Currently, there are no data concerning the link between the NER DNA repair genes polymorphisms and susceptibility to leukemia in Tunisian
population. Therefore, we investigated the association between 3 NER gene polymorphisms [XPC (Lys939Gln (rs2228001), XPD Lys 751Gln (rs13181) and XPG Asp1104His (rs17655)] and leukemia risk in a case-control study
PT ED
of a Tunisian population.
2.1. Samples
The study group consisted of 206 patients with leukemia who were diagnosed by the laboratory of molecular and cellular hematology from Pasteur Institute of Tunis,
CE
Tunisia, including 87 patients with chronic myeloid leukemia (CML), 34 patients with acute-myeloid leukemia (AML) and 85 patients with acute lymphoblastic leukemia (ALL). Eligibility criteria for cases included a newly diagnosed patient with AML,
AC
CML and ALL, clinically in steady state, and without the restriction of age and sex. Cases with other severe concomitant disease and pregnancy or patients actively breastfeeding were excluded.
For control group, there are 206 random-selected health blood donor subjects
ST
without a medical history of cancer. Controls were matched to cases by age and sex.
All subjects were Tunisians and informed consent was obtained from the participating individuals and/or their parents (patients aged
Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tunisian population K Douzi, S Ouerhani, S Menif, Ines Safra, S Abbes Doi: 10.3109/10428194.2014.974045
Leuk Lymphoma Downloaded from informahealthcare.com by Dalhousie University on 11/13/14 For personal use only.
Abstract Human DNA repair mechanisms protect the genome from DNA damage caused by endogenous and environmental agents. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely reported in different cancers. In this study we aimed to evaluate the associations between XPCLys939Gln (rs2228001), XPD Lys 751Gln (rs13181) and XPG Asp1104His (rs17655) polymorphisms and leukemia risk in the Tunisian population. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCRRFLP) in 206 leukemia patients and 206 healthy controls. We found an increased risk of leukemia among subjects carrying the XPC 939Gln/Gln genotype (OR=2.48, 95%CI=1.353 – 4.560, P=0.0042). Moreover, in subgroup analysis according to clinical types, CML patients showed a higher risk than AML and ALL patients (OR=3.87, 95%CI=1.820 – 8.237, P=0.0003). However, the XPD 751Gln allele may be protective against CML and AML development and no significant differences in genotypes frequencies were observed for XPG gene between patients and controls. Further studies with larger samples and risk factors information are needed.
© 2014 Informa UK, Ltd. This provisional PDF corresponds to the article as it appeared upon acceptance. Fully formatted PDF and full text (HTML) versions will be made available soon. DISCLAIMER: The ideas and opinions expressed in the journal’s Just Accepted articles do not necessarily reflect those of Informa Healthcare (the Publisher), the Editors or the journal. The Publisher does not assume any responsibility for any injury and/or damage to persons or property arising from or related to any use of the material contained in these articles. The reader is advised to check the appropriate medical literature and the product information currently provided by the manufacturer of each drug to be administered to verify the dosages, the method and duration of administration, and contraindications. It is the responsibility of the treating physician or other health care professional, relying on his or her independent experience and knowledge of the patient, to determine drug dosages and the best treatment for the patient. Just Accepted articles have undergone full scientific review but none of the additional editorial preparation, such as copyediting, typesetting, and proofreading, as have articles published in the traditional manner. There may, therefore, be errors in Just Accepted articles that will be corrected in the final print and final online version of the article. Any use of the Just Accepted articles is subject to the express understanding that the papers have not yet gone through the full quality control process prior to publication.
Polymorphisms in XPC, XPD and XPG DNA repair genes and leukemia risk in a Tunisian population.
K Douzi, S Ouerhani, S Menif, Ines Safra, S Abbes
Correspondence: K Douzi, Laboratory of Molecular Hematology, Pasteur Institute, P.O. Box 74, Place Pasteur, Belvedere, 1002 Tunis, Tunisia. Phone number (+216) 71 78 30 22, Fax +216 71 79 18 33. Email: [email protected] Abstract
ST
AC
CE
Human DNA repair mechanisms protect the genome from DNA damage caused by endogenous and environmental agents. Polymorphisms in DNA repair genes and differences in repair capacity between individuals have been widely reported in different cancers. In this study we aimed to evaluate the associations between XPCLys939Gln (rs2228001), XPD Lys 751Gln (rs13181) and XPG Asp1104His (rs17655) polymorphisms and leukemia risk in the Tunisian population. Genotypes were determined by polymerase chain reaction and restriction fragment length polymorphism (PCR-RFLP) in 206 leukemia patients and 206 healthy controls. We found an increased risk of leukemia among subjects carrying the XPC 939Gln/Gln genotype (OR=2.48, 95%CI=1.353 – 4.560, P=0.0042). Moreover, in subgroup analysis according to clinical types, CML patients showed a higher risk than AML and ALL patients (OR=3.87, 95%CI=1.820 – 8.237, P=0.0003). However, the XPD 751Gln allele may be protective against CML and AML development and no significant differences in genotypes frequencies were observed for XPG gene between patients and controls. Further studies with larger samples and risk factors information are needed.
Keywords: Polymorphisms; DNA repair gene; CML, AML; ALL; XPC; XPD; XPG.
JU
Leuk Lymphoma Downloaded from informahealthcare.com by Dalhousie University on 11/13/14 For personal use only.
of Tunis El Manar, Tunis, Tunisia
PT ED
Laboratory of Molecular and Cellular Hematology, Pasteur Institute of Tunis, University
1. Introduction Leukemia is a heterogeneous group of hematological malignancies; in which hematopoietic progenitor cells acquire genetic lesions that lead to a block in differentiation, increased self-renewal and unregulated proliferation. Leukemia can be either acute or chronic and they can arise from myeloid or lymphoid cell lines or both in the case of myeloid/lymphoid or mixed lineage leukemia (MLL) [1 – 4].
PT ED
Leukemia can occur at any age, however chronic leukemias are usually found in persons over 40 years of age, whereas acute leukemias are generally found in
Although mutations have long been identified as early events in carcinogenesis [7] defective DNA repair is also a risk factor for many types of cancer [8 – 10]. Unrepaired DNA damage can either result in apoptosis or DNA aberrations leading
CE
to unregulated cell growth and cancer. In order to maintain genome integrity, damage caused to DNA by various agents must be repaired and preserved throughout the life of a cell. Among DNA repair mechanisms, the Nucleotide
AC
Excision DNA Repair (NER) is one of the major DNA repair pathway, and by which bulky adducts and wide variety of deleterious DNA lesions are removed from the genome [11, 12]. NER systems recognize the DNA damage, incise the DNA strand on both sides of the lesions, remove the oligonucleotide carrying the damage and
ST
re-synthetesis the fragment [13]. Genetic polymorphisms have been described for multiple genes associated with DNA repair and may modulate gene function and alter DNA repair capacity [14, 15]. An inability to respond adequately to DNA damage or failure to repair DNA damage
JU
Leuk Lymphoma Downloaded from informahealthcare.com by Dalhousie University on 11/13/14 For personal use only.
persons less than 20 years of age [5, 6].
accurately leads to genetic instability and to an increased cancer susceptibility including leukemia [16, 17].
Currently, there are no data concerning the link between the NER DNA repair genes polymorphisms and susceptibility to leukemia in Tunisian
population. Therefore, we investigated the association between 3 NER gene polymorphisms [XPC (Lys939Gln (rs2228001), XPD Lys 751Gln (rs13181) and XPG Asp1104His (rs17655)] and leukemia risk in a case-control study
PT ED
of a Tunisian population.
2.1. Samples
The study group consisted of 206 patients with leukemia who were diagnosed by the laboratory of molecular and cellular hematology from Pasteur Institute of Tunis,
CE
Tunisia, including 87 patients with chronic myeloid leukemia (CML), 34 patients with acute-myeloid leukemia (AML) and 85 patients with acute lymphoblastic leukemia (ALL). Eligibility criteria for cases included a newly diagnosed patient with AML,
AC
CML and ALL, clinically in steady state, and without the restriction of age and sex. Cases with other severe concomitant disease and pregnancy or patients actively breastfeeding were excluded.
For control group, there are 206 random-selected health blood donor subjects
ST
without a medical history of cancer. Controls were matched to cases by age and sex.
All subjects were Tunisians and informed consent was obtained from the participating individuals and/or their parents (patients aged
