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.

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.

The incidence of breast cancer (BC) and ovarian cancer (OC) has increased in Saudi Arabia. The western region of Saudi Arabia presents a unique population with distinct genetic backgrounds, making it vital to investigate the prevalence of BC/OC-associated gene mutations in this area. This study aimed to determine the prevalence and mutational profiles of BC and/or OC predisposing genes in the western region of Saudi Arabia, and to characterize the associated phenotypes in individuals carrying these mutations. We employed next-generation sequencing (NGS) to identify the mutational spectra of 209 Saudi Arabian patients with BC and/or OC from the Western region. 51/209 (24.4%) patients had a mutation in one of the BC/OC predisposing genes. Overall, 34, 10, and 7 PV/LPV were identified in BRCA1, BRCA2, and other genes, respectively. Mutations in BRCA1 were predominant and strongly related to high-grade, triple-negative BC. BRCA1 NM_007294.4:c.1140dup p.(Lys381Glufs*3), NM_007294.4:c.5095C > T p.(Arg1699Trp), NM_007294.4:c.4986 + 6 T > C (p.?), NM_007294.4:c.5251C > T p.(Arg1751*), and NM_007294.4:c.5067_5074 + 1del p.(Met1689Ilefs*3) were recurrent with NM_007294.4:c.3217_3218del p.(Gly1073*), NM_007294.4:c.5067_5074 + 1del p.(Met1689Ilefs*3), and NM_007294.4:c.5234del p.(Asn1745Thrfs*20) being novel. The combined frequency of recurrent mutations in BRCA1 was 42%. Concerning BRCA2, we identified a recurrent variant NM_000059.4:c.7480C > T p.(Arg2494*) and two novel variants NM_000059.4:c.643del p.(Glu215Lysfs*15) and NM_000059.4: EXon1-8del. In our study, we identified a high prevalence of BRCA1/2 variants in the western region of Saudi Arabia, offering novel and important insights specific to this area. We also identified other gene variants, though their impact remains unclear due to the limited sample size. This work represents an important first step in understanding the genetic factors contributing to breast and ovarian cancer in the Western region. It underscores the urgent need for larger studies to comprehensively explore the genetic landscape and better understand how these variants influence cancer risk in this population.

Background: Melanoma, a highly aggressive skin cancer, is strongly linked to ultraviolet (UV) exposure. Despite high UV levels in Saudi Arabia, public awareness and adherence to melanoma preventive behaviours remain underexplored. This study assessed knowledge (factual accuracy), attitudes, and sun‐protective practices among adults in the western region of Saudi Arabia, investigating demographic and gender‐specific differences. Methods: A cross‐sectional online survey was conducted from April to May 2024, recruiting 553 participants aged 18–80 years through convenience sampling. A validated 46‐item questionnaire assessed melanoma knowledge, risk perception, sun exposure patterns, and adherence to preventive behaviours. Descriptive statistics and one‐way ANOVA were used to analyse differences based on age, gender, education, employment, and healthcare affiliation. Results: Moderate awareness of melanoma was observed (mean = 2.28, 5‐point Likert scale), with 73.2% of participants recognising sunlight as a risk factor for skin cancer. However, misconceptions were widespread, including beliefs that short‐term sun exposure is harmless (36%) and that sunscreen is unnecessary on cloudy days (43.8%). Females and younger participants (18–35 years) demonstrated significantly higher knowledge ( p < 0.001 and p = 0.036, respectively) and risk perception; however, adherence to sun‐protective behaviours (e.g., sunscreen re‐application, protective clothing) was suboptimal across all groups (mean = 2.67). Education level influenced awareness ( p = 0.031), but did not impact behaviour. Conclusion: Despite moderate awareness, significant knowledge gaps and a knowledge–action gap hinder melanoma prevention in this high‐UV region. Culturally tailored interventions targeting misconceptions and behavioural barriers, particularly among males and individuals with lower educational attainment, are essential. These findings inform the development of evidence‐based strategies to reduce melanoma risk in Saudi Arabia and similar high‐UV settings.

Background: The landscape of oncology varies across countries and regions, and in consanguineous populations such as Saudi Arabia, the clinical management of hereditary cancers poses a distinct challenge. Hereditary breast cancer (HBC), which is a significant public health concern, accounts for approximately 5%–10% of all breast cancer cases. High-risk genes, including BRCA1, BRCA2, PALB2, TP53 and PTEN, with germline pathogenic or likely pathogenic variants (PVs/LPVs), substantially increase the risk of breast cancer and other malignancies.Method: In this review, we explore the guidelines and the literature to present a comprehensive investigation of the genetic landscape of hereditary cancer syndromes, provide pivotal insights into disease mechanisms and inform precise clinical intervention. Given their marked therapeutic heterogeneity, a tailored precision medicine approach, rather than a uniform strategy of a one-size-fits-all model, is necessary. For high-risk breast cancer patients in Saudi Arabia, the detection rates of PVs/LPVs have reached 24%, underscoring the relevance of targeted interventions.Results: A comprehensive framework for the management of HBCs is outlined, which focuses on consanguineous populations and adapts global guidelines. We highlight the critical roles of genetic testing in guiding personalised surveillance strategies, especially for regions where data remain limited.Conclusion: Revealing the genetic variation associated with HBCs mitigates the burden on healthcare providers and the long-term effects of HBCs on affected individuals and their families. Moreover, it is a step ahead towards personalised prevention, treatment and intervention. This knowledge will empower research and innovation in biotechnology.

Background: Cancer epidemiology differs between males and females due to variation in exposure to risk factors. Kidney cancer incidence and mortality have increased globally, yet long‐term sex‐specific trends in Saudi Arabia remain insufficiently characterised. Kidney cancer incidence in Saudi Arabia has increased steadily over time, with an average annual percentage change (APC) of 3.22% over the study period. Aim: This study aimed to analyse long‐term trends in kidney cancer burden in Saudi Arabia and to compare incidence, mortality, years of life lost (YLLs) and disability‐adjusted life years (DALYs) by sex over the period 1982–2023. Methods: A retrospective observational study was conducted using non‐overlapping data from the Saudi Cancer Registry and the Global Burden of Disease 2021 study. Adults aged 20 years and older diagnosed with kidney cancer between 1982 and 2023 were included. Age‐standardised incidence, mortality, YLLs and DALYs were analysed by sex. Temporal trends were assessed using log‐linear regression models and APC was calculated. Results: A cumulative total of 34 247 adult kidney cancer cases was identified between 1982 and 2023. Over the 42‐year period, incidence increased by 3.22% annually. The increase was faster in females than in males (3.65% vs. 2.99%, p < 0.001). YLLs rose by 1.45% per year and DALYs by 1.73%, both showing greater increases among females. Despite this, the overall burden remained consistently higher in males across all indicators. Disease burden increased progressively with age and was highest in older adult populations. Conclusion: Kidney cancer burden has increased substantially in Saudi Arabia over the past four decades. Although males experience a higher overall burden, females show a faster rate of increase. These findings highlight the need for sex‐specific prevention strategies, improved early detection, and strengthened national surveillance. Addressing modifiable risk factors such as smoking, obesity and hypertension remains a priority for public health intervention.