Investigating the prevalence of pathogenic variants in Saudi Arabian patients with familial cancer using a multigene next generation sequencing panel.

Family history is an important factor in determining hereditary cancer risk for many cancer types. The emergence of next-generation sequencing (NGS) has expedited the discovery of many hereditary cancer susceptibility genes and the development of rapid, affordable testing kits. Here, a 30-gene targeted NGS panel for hereditary cancer risk assessment was tested and validated in a Saudi Arabian population. A total of 310 subjects were screened, including 57 non-cancer patients, 110 index patients with cancer and 143 of the cancer patients' family members, 16 of which also had cancer. Of the 310 subjects, 119 (38.4%) were carriers of pathogenic or likely pathogenic variants (PVs) affecting one or more of the following genes: TP53, ATM, CHEK2, CDH1, CDKN2A, BRCA1, BRCA2, PALB2, BRIP1, RAD51D, APC, MLH1, MSH2, MSH6, PMS2, PTEN, NBN/NBS1 and MUTYH. Among 126 patients and relatives with a history of cancer, 49 (38.9%) were carriers of PVs or likely PVs. Two variants in particular were significantly associated with the occurrence of a specific cancer in this population (APC c.3920T>A - colorectal cancer/Lynch syndrome (p = 0.026); TP53 c.868C>T; - multiple colon polyposis (p = 0.048)). Diverse variants in BRCA2, the majority of which have not previously been reported as pathogenic, were found at higher frequency in those with a history of cancer than in the general patient population. There was a higher background prevalence of genetic variants linked to familial cancers in this cohort than expected based on prevalence in other populations.

Increased Prevalence of EBV Infection in Nasopharyngeal Carcinoma Patients: A Six-Year Cross-Sectional Study.

Epstein Barr Virus (EBV) is implicated in the carcinogenesis of nasopharyngeal carcinoma (NPC) and currently associated with at least 1% of global cancers. The differential prognosis analysis of NPC in EBV genotypes remains to be elucidated. Medical, radiological, pathological, and laboratory reports of 146 NPC patients were collected retrospectively over a 6-year period between 2015 and 2020. From the pathology archives, DNA was extracted from tumor blocks and used for EBV nuclear antigen 3C (EBNA-3C) genotyping by nested polymerase chain reaction (PCR). We found a high prevalence of 96% of EBV infection in NPC patients with a predominance of genotype I detected in 73% of NPC samples. Histopathological examination showed that most of the NPC patients were in the advanced stages of cancer: stage III (38.4%) or stage IV-B (37.7%). Only keratinized squamous cell carcinoma was significantly higher in EBV negative NPC patients compared with those who were EBV positive (OR = 0.01, 95%CI = (0.004-0.32; p = 0.009)), whereas the majority of patients (91.8%) had undifferentiated, non-keratinizing squamous cell carcinoma, followed by differentiated, non-keratinizing squamous cell carcinoma (7.5%). Although NPC had metastasized to 16% of other body sites, it was not associated with EBV infection, except for lung metastasis. A statistically significant reverse association was observed between EBV infection and lung metastasis (OR = 0.07, 95%CI = (0.01-0.51; p = 0.008)). Although 13% of NPC patients died, the overall survival (OS) mean time was 5.59 years. Given the high prevalence of EBV-associated NPC in our population, Saudi could be considered as an area with a high incidence of EBV-associated NPC with a predominance of EBV genotype I. A future multi-center study with a larger sample size is needed to assess the true burden of EBV-associated NPC in Saudi Arabia.

Colorectal Cancer in Saudi Arabia: The Way Forward.

Colorectal cancer is the most common cancer in Saudi males and the second most common cancer in Saudi females with increasing incidence throughout the last four decades. Although the disease incidence is on the rise, still there is no systemic screening for colorectal cancer in the Saudi population. Early onset colorectal cancer is common in the Saudi population and up to 50% in Saudi patients diagnosed at late stages with regional and distal metastasis. Therefore, more efforts are required to control the disease in the Kingdom of Saudi Arabia. In this regard,  systematic work at national level is highly required to make  colorectal cancer screening for population at risk part of the routine primary health care activities. This paper highlights the current situation of colorectal cancer in the Kingdom of Saudi Arabia with relation to incidence, mortality and morbidity in addition to the disease control efforts going on. Finally, some recommendations are provided to strengthen the control program of colorectal cancer.

Utility of Circulating Cell-Free DNA in Assessing Microsatellite Instability and Loss of Heterozygosity in Breast Cancer Using Human Identification Approach.

The diagnostic and prognostic utility of circulating cell-free DNA (cfDNA) in breast cancer (BC) patients was recently reported. Here, we investigated the use of cfDNA to examine microsatellite instability (MSI) and loss of heterozygosity (LOH) for early BC diagnosis. cfDNA and genomic DNA from 41 female BC patients and 40 healthy controls were quantified using NanoDrop spectrophotometry and real-time PCR. The stability of genomic and cfDNA was assessed using a high-resolution AmpFlSTR MiniFiler human identification kit. Significant increases in cfDNA plasma concentrations were observed in BC patients compared to controls. The genotype distribution of the eight autosomal short tandem repeat (STR) loci D7S820, D13S317, D21S11, D2S1338, D18S51, D16S539, FGA, and CSF1PO were in Hardy-Weinberg equilibrium. Significant differences in the allele frequencies of D7S820 allele-8, D21S11 allele-29, allele-30.2, allele-32.2, and CSF1PO allele-11 were seen between BC patients and controls. LOH and MSI were detected in 36.6% of the cfDNA of patients compared to genomic DNA. This study highlights the utility of plasma-derived cfDNA for earlier, less invasive, and cost-effective cancer diagnosis and molecular stratification. It also highlights the potential value of cfDNA in molecular profiling and biomarkers discovery in precision and forensic medicine.

Identification of Novel Mutations in Colorectal Cancer Patients Using AmpliSeq Comprehensive Cancer Panel.

Biomarker discovery would be an important tool in advancing and utilizing the concept of precision and personalized medicine in the clinic. Discovery of novel variants in local population provides confident targets for developing biomarkers for personalized medicine. We identified the need to generate high-quality sequencing data from local colorectal cancer patients and understand the pattern of occurrence of variants. In this report, we used archived samples from Saudi Arabia and used the AmpliSeq comprehensive cancer panel to identify novel somatic variants. We report a comprehensive analysis of next-generation sequencing results with a coverage of >300X. We identified 466 novel variants which were previously unreported in COSMIC and ICGC databases. We analyzed the genes associated with these variants in terms of their frequency of occurrence, probable pathogenicity, and clinicopathological features. Among pathogenic somatic variants, 174 were identified for the first time in the large intestine. APC, RET, and EGFR genes were most frequently mutated. A higher number of variants were identified in the left colon. Occurrence of variants in ERBB2 was significantly correlated with those of EGFR and ATR genes. Network analyses of the identified genes provide functional perspective of the identified genes and suggest affected pathways and probable biomarker candidates. This report lays the ground work for biomarker discovery and identification of driver gene mutations in local population.

Impact of the COVID-19 Pandemic on Oncologists: Results of an International Study.

PURPOSE: As frontline workers facing the COVID-19 pandemic, healthcare providers should be well-prepared to fight the disease and prevent harm to their patients and themselves. Our study aimed to evaluate the knowledge, attitude, and practice of oncologists in response to the COVID-19 pandemic and its impact on them. METHODS: A cross-sectional study was conducted using a validated questionnaire disseminated to oncologists by SurveyMonkey. The tool had 42 questions that captured participants' knowledge, attitude, and practice; their experiences; and the pandemic's impact on various aspects of their lives. Participants from Middle East and North African countries, Brazil, and the Philippines completed the electronic survey between April 24 and May 15, 2020. RESULTS: Of the 1,010 physicians who participated in the study, 54.75% were male and 64.95% were medical or clinical oncologists. The level of knowledge regarding the prevention and transmission of the virus was good in 52% of participants. The majority (92%) were worried about contracting the virus either extremely (30%) or mildly (62%), and 84.85% were worried about transmitting the virus to their families. Approximately 76.93% reported they would take the COVID 19 vaccine once available, with oncologists practicing in Brazil having the highest odds ratio of intention to receive the COVID-19 vaccine (odds ratio, 11.8, 95% CI, 5.96 to 23.38, P < .001). Participants reported a negative impact of the pandemic on relations with coworkers (15.84%), relations with family (27.84%), their emotional and mental well-being (48.51%), research productivity (34.26%), and financial income (52.28%). CONCLUSION: The COVID-19 pandemic has adverse effects on various personal and professional aspects of oncologists' lives. Interventions should be implemented to mitigate the negative impact and prepare oncologists to manage future crises with more efficiency and resilience.

Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study.

Glioblastoma is a fast-growing primary brain tumor observed in adults with the worst prognosis. Preclinical studies have demonstrated the encouraging anticancer activity of statins. This study evaluated the efficacy of atorvastatin in combination with standard therapy in patients with glioblastoma. In this prospective, open-label, single-arm, phase II study, patients were treated with atorvastatin in combination with the standard glioblastoma therapy comprising radiotherapy and temozolomide. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Among 36 patients enrolled from January 2014 to January 2017, the median age was 52 (20-69) years; 22% of the patients were aged ≥60 years, and 62% were male. Patients received atorvastatin for a median duration of 6.2 (0.3-28) months. At a median follow-up of 19 months, the PFS-6 rate was 66%, with a median PFS of 7.6 (5.7-9.4) months. In terms of Grade ≥ 3 hematological adverse events, thrombocytopenia and neutropenia occurred in 7% and 12% of patients, respectively. In multivariate analyses, high baseline low-density lipoprotein levels were associated with worse survival (P = 0.046). Atorvastatin was not shown to improve PFS-6. However, this study identified that high low-density lipoprotein levels are an independent predictor of poor cancer-related outcomes. Future clinical trials testing statins should aim to enroll patients with slow-growing tumors.Clinical trial information: NCT0202957 (December 12, 2013).

Risk factors of colorectal cancer among Saudi Population: Case-control study.

BACKGROUND: Colorectal cancer (CRC) incidence and related mortalities have been steadily increasing in KSA over the past 20 years. CRC in the Kingdom of Saudi Arabia (KSA) population presents in younger ages and in more advanced disease states as compared to other countries. This study was aimed to determine factors (demographic, habitual, environmental, nutritional, and genetic) associated with CRC in Riyadh, KSA. MATERIALS AND METHODS: A matched case-control study conducted in the major hospitals in Riyadh (King Khalid university Hospital, King Faisal Specialist Hospital, Riyadh Military Hospital, Security Force Hospital, King Fahd Medical City). Here most of CRC cases are managed. The cases (n = 121) group included all recently diagnosed and pathologically confirmed Saudi cases of CRC identified during the period 1st of January 2017 till 31st of December 2018 who agreed to participate and fulfilled the inclusion criteria. A similar number of controls attending the study settings were selected consecutively from the clinics where cases were managed and matched on a 1:1 basis with cases based on age (+/-3 years) and gender. Data were collected using a structured questionnaire. Conditional logistic regression models were fitted to determine factors associated with risk of CRC. RESULT: This study included similar number of males and females in both groups: males 69 (57%) and females 52 (43%) in each group (Chi-square test P = 1.0). The mean (S.D) age in the cases group was 53.6 (S.D = 12.9) and 53.3 (S.D = 12.9) in the controls group (Student test P = 0.86). In the final multivariate conditional logistic regression model, variables independently associated with risk of colorectal cancer were body mass index (OR = 0.93; 95% CI 0.87-0.98; P = 0.011) employment status (inverse relation: OR = 0.33; 95% CI 0.14-0.77; P = 0.010), colon polyps (OR = 4.09; 95% CI 1.06-15.82; P = 0.041), and constipation (OR = 4.98; 95% CI 1.91-15.99; P = 0.001). CONCLUSION: Factors associated with CRC in the major referral hospitals in KSA were colon polyps, chronic constipation, and unemployment. These factors should be considered when screening for patients at risk for CRC.

The Use of Ziziphus spina-christi Extract in Treating Erlotinib (Tarceva®) Associated Rash: A Case Report.

The most common side effect for cancer patients using epidermal growth factor receptor inhibitors (EGFRI) is the development of an itchy papulopustular rash. In severe cases, the patients are forced to stop taking the medications, hence affecting treatment outcomes. We herein report a case of a 50-year-old patient who developed a papulopustular rash after starting erlotinib. He treated himself with Ziziphus spina-christi leaves which is a plant well known for its anti-inflammatory and antibacterial properties in the middle east. We hypothesize that the anti-inflammatory, soothing, and antibacterial activity of the Ziziphus tree might actually represent a possible better treatment of the rash than available treatments, particularly in patients on EGFR blockers, and hence improve treatment outcomes.

Management and treatment recommendations for World Health Organization Grade III and IV gliomas.

The treatment recommendations provided in this manuscript are intended to serve as a knowledge base for clinicians and health personals involved in treating patients with high-grade malignant glioma. In newly diagnosed patients, complete resection or biopsy is required for histological characterization of the tumor, which in turn is essential to decide the treatment strategy. In patients with good or borderline performance score, radiotherapy (RT), and chemotherapy are the preferred management. In patients with poor performance score, RT with best possible supportive care is the mainstay of the management. All patients have to undergo brain magnetic resonance imaging procedure quarterly or half-yearly for 5 years and then on an annual basis. In patients with recurrent malignant glioma, wherever possible re-resection or re-irradiation or chemotherapy can be considered along with supportive and palliative care. High-grade malignant glioma should be managed in a multidisciplinary center with the best of the possible care that is available based on the evidence as discussed in this manuscript.