The Application of Clinical Genetics (Jun 2020)
The Impact of the Genetic Polymorphism in DNA Repair Pathways on Increased Risk of Glioblastoma Multiforme in the Arab Jordanian Population: A Case–Control Study
Abstract
Sohaib M Al-Khatib,1 Nour Abdo,2 Laith N Al-Eitan,3 Abdel-Hameed W Al-Mistarehi,4 Deeb Jamil Zahran,5 Marwan Al Ajlouni,2 Tariq Zuheir Kewan6 1Department of Pathology and Laboratory Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 2Department of Public Health, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 3Department of Biotechnology and Genetic Engineering, Faculty of Science and Arts, Jordan University of Science and Technology, Irbid, Jordan; 4Department of Family Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 5Department of Internal Medicine, Faculty of Medicine, Jordan University of Science and Technology, Irbid, Jordan; 6Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USACorrespondence: Sohaib M Al-KhatibDepartment of Pathology and Laboratory Medicine, Jordan University of Science and Technology, P.O.Box 3030, Irbid 22110, JordanTel +962-799-409933Fax +962-2-72006262Introduction: Among the Jordanian population, brain tumors are the tenth most common type of cancers in both males and females, comprising 2.8% of all newly diagnosed neoplasms. Diffuse gliomas are the most prevalent and the most aggressive primary brain tumors in adults. The incidence of diffuse gliomas varies among different populations; this variation is partially linked to genetic polymorphisms. The purpose of the study is to examine the association between (BRCA1 rs799917G>A, rs1799966T>C, EXO1 rs1047840G>A, EME1 rs12450550T>C, ERCC2 rs13181T>G, rs1799793C>T, and XRCC1 rs1799782G>A) DNA repair gene polymorphisms and glioblastoma multiforme (GBM) susceptibility, and survival in the Jordanian Arab population.Methods: Eighty-four patients diagnosed with glioblastoma multiforme at the King Abdullah University Hospital (KAUH) between 2013 and 2018 and 225 healthy cancer-free control subjects with similar geographic and ethnic backgrounds to the patients were included in the study. Genomic DNA was extracted from the formalin-fixed paraffin-embedded tissues of the subjects. The Sequenom MassARRAY® sequencer system (iPLEX GOLD) was used. The analyses included assessments of population variability and survival.Results: This study is the first to address the relationship between BRCA1 rs1799966 and rs799917 SNP, and the risk of GBM among the Arab Jordanian population. The findings of the study show that BRCA1 rs799917 is associated with decreased risk of GBM in the recessive model (AA vs G/G-A/G: OR, 0.46, 95% CI, 0.26– 0.82, p=0.01) and the same SNP is associated with increased risk of GBM in the overdominant model (AG vs G/G-A/A: OR, 1.72, 95% CI, 1.02– 2.89, p=0.04).Keywords: glioblastoma multiforme, DNA repair genes, SNP, overall survival, Arab population
