Genetic variations in CYP2A6, CYP2E1, GSTM1, GSTT1 genes and the risk of Nasopharyngeal carcinoma in North African population.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a multifactorial malignancy associated with both genetic and environmental factors. Polymorphic deletions of the phase I and phase II genes involved in the detoxification of potential carcinogens may be a risk factor for nasopharyngeal carcinoma. In this study, we investigated the relationship between CYP2E1 (rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) gene variations and NPC risk in North African countries with the highest incidence of NPC (Morocco, Algeria and Tunisia). and the evaluation of the potential use of these variants as potential biomarkers for NPC management. METHODS: A total of 600 NPC cases and 545 controls frequency-matched on ethnicity, sex, age and childhood household type, were recruited from three North African countries (Morocco, Algeria and Tunisia) and analysed. Genotyping of CYP2A6 and CYP2E1(rs3813867) was performed by polymerase chain reaction restriction (PCR)-fragment length polymorphism (RFLP) analysis and the GSTM1 (rs1183423000) and GSTT1(rs1601993659) genetic variations were evaluated using the PCR technique. RESULTS: The genotype distributions of CYP2E1(rs3813867), CYP2A6, GSTM1(rs1183423000) and GSTT1(rs1601993659) genotypes did not differ significantly among NPC cases and controls (p > 0.05). Furthermore, our data did not reveal any association with smoking and the studied variants, even when the samples were stratified by the duration period of smoking. CONCLUSION: In this large studied North African population, our findings suggest that the functional CYP2E1, CYP2A6, GSTM1 and GSTT1 variations did not influence NPC susceptibility.

Prevalence of Polyomaviruses and Herpesviruses in Moroccan Breast Cancer.

Breast cancer (BC) is the most frequently diagnosed cancer and the leading cause of cancer death in women worldwide, accounting for 24.5% of total new cancer cases and 15.5% of total cancer deaths. Similarly, BC is the most common cancer among Moroccan women, comprising a noteworthy percentage of 40% of all cancers in women. Globally, 15% of cancers are attributable to infections; among them, viruses play a significant role. The present study aimed to explore the presence of a wide range of viral DNA in samples recovered from 76 Moroccan patients with BC and 12 controls using Luminex technology. The explored viruses were as follows: 10 polyomaviruses (PyVs): BKV, KIV, JCV, MCV, WUV, TSV, HPyV6, HPyV7, HPyV9, and SV40; and 5 Herpesviruses (HHVs): CMV, EBV1, EBV2, HSV1, and HSV2. Our results revealed the presence of PyVs DNA in both control (16.7%) and BC tissues (18.4%). Nonetheless, HHV DNA was detected exclusively in BC tissues (23.7%), with a predominance of Epstein-Barr virus (EBV) (21%). In conclusion, our study highlights the presence of EBV in human BC tissues, which may play an important role in its development and/or progression. Further investigations are needed to confirm the presence/co-presence of these viruses in BC.

Epidemiological, Clinicopathological and Prognosis Features of Moroccan Patients with Nasopharyngeal Carcinoma.

PROPOSAL: A distinct epidemiology, etiology, clinical characteristics, and therapeutic outcomes characterize nasopharyngeal carcinoma (NPC) from other head and neck cancers. An actualized analysis of NPC patients' features enables a global view of NPC management. Accordingly, the current study investigated the epidemiological and clinical characteristics of Moroccan patients with NPC, as well as their 4-years survival outcomes and influencing prognostic factors. METHODS: We prospectively analyzed data of 142 histologically confirmed Moroccan patients with NPC between October 2016 and February 2019. Kaplan-Meier and Cox regression analyses were used to assess predictive prognostic factors related to NPC. All analyses were conducted using SPSS version 21 statistical software. RESULTS: In the present study, a net male predominance was found, with a mean age of 44±16.3 years old. Advanced stages of NPC were observed in 64.1% of patients, and 32.4% of patients presented with distant metastasis at diagnosis. The 4-years overall survival, locoregional relapse-free survival, distant metastasis-free survival and progression-free survival were 68.0%, 63.0%, 53.9%, and 39.9%, respectively. Age, N category and distant metastasis were identified as the most important independent prognosis factors for NPC in this cohort (p<0.05). CONCLUSION: In conclusion, NPC affects young adults and is frequently diagnosed at advanced disease stages, impacting therefore negatively patients survival; which is in line with data from endemic areas for NPC. The current study clearly highlights that a greater attention should be directed to improving the management of this aggressive malignancy.

Genetic Polymorphisms in ERCC1 Gene and Their Association with Response to Radiotherapy in Moroccan Patients with Nasopharyngeal Carcinoma.

OBJECTIVE: Nasopharyngeal carcinoma (NPC) is a severe malignant disease. Despite its low frequency, NPC is very common in North African population. Radiotherapy is the standard therapeutic treatment of NPC. However, radioresistance hampers the success of treatment. At the molecular scale, radioresistance is due to genetic variations involved in DNA repair pathways in NPC patients. Several studies reported that single nucleotide polymorphisms (SNPs) in excision repair cross complementing group 1 (ERCC1) could be associated with radioresistance. In this optic, the present study aimed to evaluate the association between DNA repair gene polymorphisms ERCC1 C8092A and ERCC1 C118T and radiotherapy response of patients with NPC. METHODS: A total of 95 patients with confirmed NPC were recruited at the Mohammed VI Center for Cancer Treatment, Casablanca - Morocco between 2016 and 2018. Two single nucleotide polymorphisms in ERCC1 gene were genotyped. Multiple analysis software was used to assess the correlation between these SNPs and radio-therapeutic response. RESULTS: Sequencing of ERCC1 C8092A polymorphism revealed that CC and CA genotypes were found in 51.6% and 45.3% of cases, respectively, whereas the homozygote AA genotype was reported in only 3.1% of cases. For ERCC1 C118T polymorphism, the heterozygote CT genotype was identified in 49.5% of cases. Homozygotes genotypes CC and TT were detected in 17.9% and 32.6% respectively of NPC cases. Of note, no significant association was found between the ERCC1 C8092A polymorphism and response to radiation therapy (p=0.81). Similarly, there was no significant association between the response to radiotherapy and allelic distribution (p=0.56). Likewise, no correlation was observed neither with genotypes (p=0.07) nor with alleles (p=0.09) of ERCC1 C118T polymorphism and response to radiation therapy. CONCLUSION: Our results clearly showed that ERCC1 C8092A and ERCC1 C118T polymorphisms were not associated with response to radiotherapy in Moroccan NPC patients. Large studies are warranted to confirm the role of these SNPs in therapeutic response of NPC patients.

Pretreatment [18F]FDG PET/CT and MRI in the prognosis of nasopharyngeal carcinoma.

OBJECTIVE: The present study aimed to assess the prognostic interest of metabolic and anatomic parameters derived from 2-deoxy-2-[18F]fluoro-D-glucose positron emission tomography/computed tomography ([18F]FDG PET/CT) and head and neck magnetic resonance imaging (HN-MRI) for better management of nasopharyngeal carcinoma (NPC). METHODS: In this study, pre-treatment [18F]FDG PET/CT and HN-MRI parameters of NPC patients diagnosed between January 2017 and December 2018, were prospectively investigated. Correlation between those parameters and 4-year patient's survival outcomes was evaluated using Kaplan-Meier and Cox-regression analyses. RESULTS: Our results revealed a significant association between pre-treatment nodal-maximum standardized uptake value (N-SUV max) and N categories (p = 0.01), between pre-treatment node-to-tumor SUV ratio (NTR) and both tumor size (p = 0.01) and N categories (p = 0.009), as well as between metabolic tumor volume (MTV) and both tumor size and NPC overall stage (p < 0.000). In multivariate analyses, pre-treatment N-SUV max, NTR and MTV were significant independent predictors of overall survival, distant metastasis-free survival, and progression-free survival (PFS) (p < 0.05). N-SUV max and MTV were also found to be significant independent predictors of loco-regional recurrence-free survival (p < 0.05), whereas HN-MRI detection of skull-base bone invasion was an independent factor associated with worse PFS in NPC (p = 0.03). CONCLUSIONS: The present study highlights N-SUV max, NTR and MTV derived from [18F]FDG PET/CT, and skull-base bone invasion defined by HN-MRI, as promising metabolic and anatomic prognosis biomarkers for NPC.

Anthropometric Assessment of General and Central Obesity in Urban Moroccan Women.

In the last few decades, North African countries have faced the nutrition transition, leading to an increase in obesity, exacerbated by an extremely low rate of physical activity (PA). Particular attention must be paid to abdominal obesity (one of the metabolic syndrome criteria), which has been linked to several health problems. The present study aims to investigate the prevalence of overweight/obesity, particularly abdominal obesity, in a sample of urban Moroccan women and to analyze the anthropometric indicators of metabolic syndrome risk among subsamples with different PA and socio-demographic characteristics. Urban Moroccan women living in Casablanca (n = 304; mean age 37.4 ± 15.6 years) were recruited for this cross-sectional study. Data concerning socio-demographic variables, PA behavior, and anthropometric measures (height, weight, waist, and hip circumferences) were directly collected. Body mass index, waist-to-hip ratio, waist-to-height ratio, and relative fat mass were computed. Comparisons between women with different socio-demographic characteristics were performed through ANCOVA adjusted for age. The results reveal that 39.4% of the women did not practice any PA. The percentage of women above the cutoffs of risk for general and central obesity was more than half for all the indexes, except for waist-to-hip ratio (WHR), and 19.6% were at a very high risk of health issues. Moreover, being female unmarried, childless, graduates, and students were found to be protective against obesity. In conclusion, Moroccan women have a high level of obesity, especially abdominal, and preventive interventions are needed to reduce the health impact of obesity in this population.

Prognostic value of Epstein-Barr virus DNA load in nasopharyngeal carcinoma: a meta-analysis.

The present meta-analysis was conducted to evaluate the prognostic value of pre and post-Epstein Barr Virus (EBV) DNA load testing and to assess the clinical benefit of using this molecular approach in the prognosis for a better nasopharyngeal carcinoma (NPC) management. Relevant studies were searched in different database until May 2020. Patient´s outcomes overall survival (OS), disease free survival (DFS), progression-free survival (PFS), distant-metastasis-free survival (DMFS), and local-regional-failure-free survival (LRFS), hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted from selected studies. The association of pre and post-EBV DNA load and survival outcomes was assessed using review manager and the pooled HRs with 95% CIs were calculated. Twenty-six eligible studies were included in this meta-analysis, with a total of 9966 patients. Pooled HRs showed that EBV DNA levels before and after treatment are significantly associated with survival outcomes, with HR (95% CI) of 2.09 [1.74, 2.51] for OS, 1.77 [1.19, 2.62] for DFS, 2.53 [2.18, 2.92] for DMFS, 1.78 [1.45, 2.19] for LRFS and 2.17 [1.91, 2.47] for PFS in pre-EBV DNA, and an HR (95%) of 4.52 [2.44, 8.36], 4.08 [2.38, 6.99], 5.59 [ 3.58, 8.71] and 8.88 [5.29, 14.90] for OS, DFS and PFS and DMFS in post-EBV DNA, respectively. High pre and post-EBV DNA levels were significantly associated with poor NPC patient´s survival outcomes; which clearly confirm the high interest to introduce viral EBV DNA load as a prognostic biomarker for NPC management.

The Dynamic Change in Plasma Epstein-Barr Virus DNA Load over a Long-Term Follow-Up Period Predicts Prognosis in Nasopharyngeal Carcinoma.

The current study was designed to investigate the changes in the circulating Epstein−Barr virus DNA load (EBV DNA) at various time points before and after treatment and its clinical significance in nasopharyngeal carcinoma (NPC). A total of 142 patients with NPC were prospectively enrolled in this study. The plasma EBV DNA concentration was measured before and after treatment using qPCR. The prognostic values of the EBV DNA load were analyzed using the Kaplan−Meier and Cox regression tests. Following multivariate analysis, our data showed that high pre-EBV DNA loads were associated with significantly poorer distant metastasis free survival (DMFS) and progression free survival (PFS); detectable end-EBV DNA loads were associated with significantly worse loco-regional recurrence free survival (LRRFS) and PFS, and the detecTable 6 months-post-EBV DNA loads were associated with significantly poorer overall survival (OS), DMFS and PFS (p < 0.05). Additionally, combining the pre-EBV DNA load and the stage of the disease, our results showed that patients at stage III-IVA with a low pre-EBV DNA load had similar survival rates as patients at stage II with a low or high pre-EBV DNA load, but had better survival rates than those at stage III-IVA with a high pre-EBV DNA load. Taken together, we showed that the change of the EBV DNA load measured at several time points was more valuable than at any single time point for predicting patients' survival for NPC. Furthermore, combining the pre-EBV DNA load and the TNM classification could help to formulate an improved prognostic model for this cancer.

Circulating cell-free epstein-barr virus DNA levels and clinical features in Moroccan patients with nasopharyngeal carcinoma.

BACKGROUND: The identification of effective prognosis biomarkers for nasopharyngeal carcinoma (NPC) is crucial to improve treatment and patient outcomes. In the present study, we have attempted to evaluate the correlation between pre-treatment plasmatic Epstein-Barr virus (EBV) DNA load and the conventional prognostic factors in Moroccan patients with NPC. METHODS: The present study was conducted on 121 histologically confirmed NPC patients, recruited from January 2017 to December 2018. Circulating levels of EBV DNA were measured before therapy initiation using real-time quantitative PCR. RESULTS: Overall, undifferentiated non-keratinizingcarcinoma type was the most common histological type (90.1 %), and 61.8 % of patients were diagnosed at an advanced disease stage (IV). Results of pre-treatment plasma EBV load showed that 90.9 % of patients had detectable EBV DNA, with a median plasmatic viral load of 7710 IU/ml. The correlation between pre-treatment EBV DNA load and the conventional prognostic factors showed a significant association with patients' age (p = 0.01), tumor classification (p = 0.01), lymph node status (p = 0.003), metastasis status (p = 0.00) and overall cancer stage (p = 0.01). Unexpectedly, a significant higher level of pre-treatment EBV DNA was also found in plasma of NPC patients with a family history of cancer (p = 0.04). The risk of NPC mortality in patients with high pretreatment EBVDNA levels was significantly higher than that of those with low pre-treatment plasma EBV-DNA levels (p < 0.05). Furthermore, patients with high pre-treatment EBV-DNA levels (≥ 2000, ≥ 4000) had a significant low overall survival (OS) rates (p < 0.05). Interestingly, lymph node involvement, metastasis status and OS were found to be the most important factors influencing the EBV DNA load in NPC patients. CONCLUSIONS: The results of the present study clearly showed a high association between pre-treatment EBV DNA load, the crucial classical prognostic factors (T, N, M and disease stage) of NPC and OS, suggesting that pre-treatment EBV DNA can be a useful prognostic biomarker in clinical decision-making and improving NPC treatment in Morocco.