Prevalence of RNASEL, ELAC2 and MSR1 gene mutations among prostate cancer patients in Palestine

Discussion Committee: 
Dr. Ashraf Sawafta / Supervisor
Dr. Majdi Dwikat /Co-supervisor
Dr. Hilal Zaid External examiner
Dr. Amjad I.A. Hussein /Internal examiner
Dr. Ashraf Sawafta / Supervisor
Dr. Majdi Dwikat /Co-supervisor
Esra’a Al Hamad
Prostate cancer (PC) is considered as a second prevalent cancer type among males in Palestine. Genetic background is the most common leading for PC. A family history with PC increase possibility for offspring to develop this disease for more than three folds. The mean age of diagnosis of PC is 71 ± 6 years, for a male with no family genetic background for PC . However a man who has a family history could be diagnosed before the age of 60. RNASEL, ELAC2 and MSR1 are susceptible genes that play an important role in hereditary prostate cancer (HPC). E265X mutation in RNASEL, (Ser217Leu and Ala541Thr) mutations in ELAC2, and (P275A)in MSR1are founder mutations associated with (HPC). The aim of this study is to investigate the prevalence of these four mutations in Palestinian PC patients and non PC males in order to establish a genetic profile, and to identify healthy people with high risk for PC. Therefore identification and characterization of these genes will be a key step for improving the detection and treatment of prostate cancer. For this purpose 50 blood samples were obtained from 38 PC patients and 12 healthy relatives from different cities of the West Bank. The DNA was extracted from each blood sample; and amplified by PCR. The mutational screening were performed by two types of techniques; Restriction fragment length polymorphism (RFLP) which performed for all samples to find the mutations of ELAC2 (Ser217Leu and Ala541Thr), and DNA sequencing was performed for 15 samples (the first 15 samples were collected) to find the mutations of RNASEL (E265X) and MSR1 (P275A). The mutation Ser217Leu was found in 23 subjects out of the 50 tested; 19 of them have heterozygous genotype from both patients and healthy carriers with (38% incidence rate), and 4 patients have homozygous genotype with (8% incidence rate). While Ala541Thr mutation was found in 3 patients; 2 of them have heterozygous genotype with (4% incidence rate), and only 1 of them have homozygous genotype with (2% incidence rate). Patients with Ala541Thr mutation are also carrying Ser217Leu mutation. The results of sequencing of 15 samples for screening RNASEL (E265X) and MSR1 (P275A) shown that only one carrier have homozygous genotype of (E265X), and two other carriers have heterozygous genotype of (P275A). In conclusion a number of potential genetic risk factors for prostate cancer have been identified which may in near future contribute to earlier diagnosis of prostate cancer so that earlier treatment can be started. The mutations identified in this study might lead to the development of new strategies in PC treatment. Further studies of genotype/phenotype correlations in these mutations and other susceptibility mutations in PC and the healthy people with high risk are needed in order to support these results.
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