Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis.
Lactose intolerance is a condition causing an inability to absorb and digest lactose leading to gastrointestinal symptoms such as abdominal pain, diarrhea, and flatulence. Because of the similarities between lactose intolerance and cow's milk allergy, it is becoming necessary to increase physicians' understanding of these two diseases. Consequently, we aimed to determine the level of knowledge of lactose intolerance and cow's milk allergy among medical students. An electronic survey was distributed to 399 medical students at two universities in Saudi Arabia from October to November 2022. The majority of the respondents had an inadequate knowledge of both lactose intolerance and cow's milk allergy (99.75% and 97.99%, respectively). According to the study's results that showed a lack of awareness among health-related students, further studies and awareness programs are highly recommended.
Background Growing knowledge supports the importance of microRNAs (miRNAs) in modulating the initiation and development of breast cancer (BC) and underlying mechanisms. BC is a significant public health in females worldwide, where it remains the leading cause of death among Saudi females. Here, we evaluate the susceptibility of the miRNA genetic variants to the risk of BC in Saudi females. Methods One hundred fifty-four females, including 76 females diagnosed with BC and 78 healthy controls, were analyzed using TaqMan™ (Thermo Fischer Scientific, Waltham, MA) genotyping assays for the miR-196a2 rs11614913 C>T, miR-146a rs2910164 C>G, and miR-499 rs3746444 A>G. We utilized the SNPStats software (https://www.snpstats.net) (Institut Català d'Oncologia, Barcelona, Spain) to choose the best interactive inheritance model for the examined miRNAs. Results The examined miRNA single-nucleotide polymorphisms (SNPs) showed no clear association with the risk of BC (P > 0.05). As for genotypic distributions, significant associations were found for the rs2910164 SNP in most interactive models of inheritance: 2.50 (95% confidence interval {CI}, 1.2-5.17; P = 0.0135) in the codominant model, 2.34 (95% CI, 1.11-4.8; P = 0.0197) in the dominant model, and 2.40 (95% CI, 1.22-4.73; P = 0.0113) in overdominant model. The rs2910164 C/G heterozygosity showed overexpression in cases compared to controls (73.7% versus 53.9%; chi-squared (χ2) = 6.5; P = 0.0109), but the homozygous rs2910164 G/G showed a significant protective effect (21.1% versus 38.5%; χ2 = 17.4; P = 0.019). The heterozygosity did not affect the risk to the BC in the two miRNAs (rs11614913 C>T and rs3746444 A>G). Conclusion Despite lacking associations with the examined miRNAs, the heterozygous genotype rs2910164 C/G can identify at-risk females. More studies should be replicated using a panel of miRNA genes to discover significant associations with the risk of BC.
Background Cancer represents a global concern as the second-leading cause of mortality worldwide. It is defined as a genetic disease that develops as a result of several genetic abnormalities and changes to specific genes. Thus, early preventive measures and clinical interventions can be implemented with impressive results using genetic testing and screening for hereditary susceptibility. Objectives The present study assessed the knowledge of cancer genetics and of the importance of genetic testing among the general population in Saudi Arabia's Makkah Province. Methods A descriptive cross-sectional study was conducted among the general population in Makkah Province. The data were collected through an online questionnaire from November 2022 through December 2022. Results The study recruited 1,329 participants, the largest group of whom were 21-30 years old (n=524, 39.4%). About 60.1% of the respondents were female. The findings reveal that 52.52% of the respondents had poor knowledge, while only 4.82% exhibited good knowledge. Conclusion Approximately half the total participants possessed an inadequate understanding of cancer genetics and the importance of genetic testing. This indicates the need for awareness campaigns and programs to improve the general population's understanding of the genetic predisposition to cancer.
[This corrects the article DOI: 10.1016/j.heliyon.2023.e13876.].
Graft versus host disease (GVHD) remains the major cause of morbidity and mortality after allogeneic stem cell transplantation, especially for intestinal GVHD, as steroid resistant GVHD results in high mortality. For this reason, new treatments of GVHD are needed. One approach is the reduction of pathogenic bacteria using anti-E. coli Immunoglobulin Yolk (IgY). In a haploidentical murine model, B6D2F1 mice conditioned with total body irradiation (TBI), received bone marrow cells (BM) and splenocytes (SC) from either syngeneic (Syn = B6D2F1) or allogeneic (Allo = C57BL/6) donors. Following this, animals received from day -2 until day +28 chow contained IgY or control chow. Thereafter the incidence and severity of aGVHD, the cytokines, chemokines, IDO1 and different pathogen-recognition receptors (PRR) were analyzed and compared to control animals (received chow without IgY). We found that animals receiving chow with IgY antibody showed reduced GVHD severity compared to control animals. On day28 after alloBMT, IDO, NOD2, TLR2, TLR4 and the inflammatory chemokine CCL3, were reduced in the colon and correlated with a significant decrease in E. coli bacteria. In summary chow containing chicken antibodies (IgY) improved GVHD via decrease in bacterial load of E coli conducting to reduction of pathogen receptors (NOD2, TLR2 and 4), IDO, chemokines and cytokines.
BACKGROUND: The PSMB8 and PSMB9 immunoproteasome genes are essential in cell processes, such as decisions on cell survival or death, the cell cycle, and cellular differentiation. Because recent evidence has demonstrated an immunological role for proteasomes in various malignancies, including urothelial bladder carcinoma (UBC), we evaluated single nucleotide polymorphisms (SNPs) in PSMB9 and PSMB8. We determined any associations between these SNPs and susceptibility to UBC in the Saudi community. METHODS: Samples of genomic DNA were taken from buccal cells of 111 patients with UBC and 78 healthy controls. TaqMan Real-Time PCR was used to determine genotype distributions and allele frequencies for the PSMB9 rs17587 G>A and PSMB8 rs2071543 G>T SNPs. We used SNPStats (https://www.snpstats.net) to choose each SNP's best interactive inheritance model. RESULTS: The PSMB9 rs17587 SNP was associated with the risk of UBC (odds ratio [OR] = 5.21, P < 0.0001). In contrast, the PSMB8 rs2071543 SNP showed no association with UBC risk (OR = 1.13, P = 0.7871). In terms of genotypic distribution, the rs17587 G>A SNP was more frequent in UBC cases than controls in both the dominant (OR = 7.5; 95% confidence interval, 3.7-15.1; P = 0.0051) and recessive (OR = 17.11, 95% confidence interval 5.1-57.4; P = 0.0026) models. Genotypic distribution of the PSMB8 rs2071543 G>T SNP was not significantly different between cases and controls in any interactive inheritance models (P > 0.05). CONCLUSION: These results suggest a potential role for PSMB9 as a biomarker for increased UBC risk. Discovering more genetic variants within immunoproteasome genes related to antigen presentation could help further our understanding of this risk.
Breast cancer is one of the rarest malignancies in males, with a low incidence rate compared to all breast cancers. Gene mutation plays a significant role in the pathologic process of cancer. Mutations in breast cancer gene 1 (BRCA1) and breast cancer gene 2 (BRCA2) have been associated with male breast cancer (MBC), as well as prostate cancer (PCa). Despite the etiopathogenetic similarity, combined MBC and PCa is a rare entity. This report presents the case of a 57-year-old male with a history of breast cancer who underwent modified radical mastectomy (MRM) with lymph node dissection followed by adjuvant chemoradiotherapy four years ago. The patient presented with recurrent episodes of voiding dysfunction for three months, followed by urine retention. His family history was positive for breast and lung cancer. High prostate-specific antigen (PSA) and Prostate Imaging-Reporting and Data System 5 (PI-RADS5) necessitate transrectal ultrasound-guided biopsy, which confirmed the diagnosis of PCa. Molecular genetics testing and next-generation sequencing (NGS) analysis identified heterozygous variant c.636T>G, p.(Tyr212*) in the checkpoint kinase 2 (CHEK2) gene. The patient is planned for neoadjuvant luteinizing hormone-releasing hormone (LHRH) for 3-6 months, to be followed by transurethral tunneling of the prostate (TUTP) with adjuvant LHRH. The allele frequency of this patient mutation was documented for the first time among the general population, and it has not been described in the literature. This unique and rare case was presented with clinical, morphological, and immunohistochemical features together with a review of the current literature.
PURPOSE: Colorectal carcinoma (CRC) represents a considerable public health burden in Saudi Arabia. Several candidate genes and genetic variants have been associated with morbidity and mortality among patients with CRC. We explored whether allelic variants of the GSTM1, GSTT1, CYP450 (rs4646903 and rs1048943), and TP53 (rs1042522) genes predisposed nonsmoking Saudi individuals to increased risk for CRC. PATIENTS AND METHODS: DNA from buccal cells of 158 participants (80 with CRC and 78 healthy controls) were analyzed for five SNPs using conventional PCR and TaqMan genotyping assays. The SNPStats software was utilized to choose the best interactive inheritance mode for selected SNPs (https://www.snpstats.net). RESULTS: The mean age of diagnosis was 62.4±13.5 years (range, 40-83 years), with those aged 71-80 years and those aged 40-50 years accounting for the most diagnoses (35.7% and 28.6% of diagnosis, respectively). The GSTM1 and TP53 rs1042522 SNPs were associated with CRC (OR= 3.7; P< 0.0001, and OR= 1.6; P= 0.033, respectively). A plausible contribution to CRC was observed for the GSTM1 and TP53 rs1042522 SNPs (x 2 Yates= 14.7; P= 0.00013, and x 2 Yates= 11.2; P= 0.0008, respectively), while the GSTT1 null variant did not affect risk. Heterozygosity in the CYP450 (rs4646903 and rs1048943 SNPs) was associated with a significant risk for CRC. The GSTM1/GSTT1 and CYP450 rs4646903/rs1048943 SNP pairs were in linkage disequilibrium, and the associations were statistically significant (P= 0.01 and P= 4.6x10â7, respectively). CONCLUSION: The GSTM1 and TP53 rs1042522 variants can increase the development of CRC in Saudi nonsmokers. Even the presence of one copy of a variant allele in the CYP1A1 gene can predispose CRC risk. Additional studies should also examine other SNP combinations with lifestyle factors that may help prevent, rather than facilitate, colorectal tumorigenesis.
BACKGROUND: The antigen processing 1 (TAP1) and proteasome 20S subunit beta 9 (PSMB9) genes are associated with strong susceptibility to many autoimmune diseases. Here, we explored whether TAP1/PSMB9 genetic variants, individually or combined, affected susceptibility to the complex, autoimmune-based skin disorder vitiligo. METHODS: Samples of genomic DNA from buccal cells of 172 patients with vitiligo and 129 healthy controls were analyzed using TaqMan™ genotyping assays for the TAP1 rs1135216 (A>G) and PSMB9 rs17587 (A>G) single nucleotide polymorphisms (SNPs). SNPStats software (https://www.snpstats.net) was utilized to choose the best interactive inheritance mode for selected SNPs. RESULTS: The genotype frequencies for the TAP1 rs1135216 and PSMB9 rs17587 SNPs were in Hardy-Weinberg equilibrium for cases (P= 0.11 and P= 0.10, respectively) but not for controls (P< 0.05). The TAP1 rs1135216 (D637G) and PSMB9 rs17587 (R60H) SNPs increased the risk of vitiligo four-fold and two-fold, respectively (odds ratio [OR]= 4.6; 95% confidence interval [CI], 3.2-6.5; P< 0.0001 and OR= 2.2; 95% CI, 1.5-3.1; P< 0.0001). The recessive model (G/G-D/G versus D/D) and the codominant model (R/R versus R/H) were the best models of inheritance for the rs113526 and rs17587 SNPs, respectively (OR= 16.4; 95% CI, 2.0-138; P= 0.0006 and OR= 1.7; 95% CI, 0.3-1.8; P= 0.013). Vulgaris, focal vulgaris, and acryl/acrofacial were the most common vitiligo subtypes in our sample (51%, 21%, and 19%, respectively). Heterozygous rs113526 (637D/G) and rs17587 (60R/H) were the most common genotypes in most vitiligo subtypes. The heterozygous 637D/G genotype and the 637G variant allele were significantly more common in patients with active disease than in patients with stable disease (P= 0.000052 and P= 0.0063, respectively). CONCLUSION: Our findings suggest a crucial role for TAP1 rs1135216 and PSMB9 rs17587 in the risk and progression of vitiligo in the Saudi community. Genomic analyses are needed to identify more candidate genes and more genetic variants associated with vitiligo.
