Geographic EBV variants confound disease-specific variant interpretation and predict variable immune therapy responses.

ABSTRACT: Epstein-Barr virus (EBV) is a potent carcinogen linked to hematologic and solid malignancies and causes significant global morbidity and mortality. Therapy using allogeneic EBV-specific lymphocytes shows promise in certain populations, but the impact of EBV genome variation on these strategies remains unexplored. To address this, we sequenced 217 EBV genomes, including hematologic malignancies from Guatemala, Peru, Malawi, and Taiwan, and analyzed them alongside 1307 publicly available EBV genomes from cancer, nonmalignant diseases, and healthy individuals across Africa, Asia, Europe, North America, and South America. These included, to our knowledge, the first natural killer (NK)/T-cell lymphoma (NKTCL) EBV genomes reported outside of East Asia. Our findings indicate that previously proposed EBV genome variants specific to certain cancer types are more closely tied to geographic origin than to cancer histology. This included variants previously reported to be specific to NKTCL but were prevalent in EBV genomes from other cancer types and healthy individuals in East Asia. After controlling for geographic region, we did identify multiple NKTCL-specific variants associated with a 7.8-fold to 21.9-fold increased risk. We also observed frequent variations in EBV genomes that affected peptide sequences previously reported to bind common major histocompatibility complex alleles. Finally, we found several nonsynonymous variants spanning the coding sequences of current vaccine targets BALF4, BKRF2, BLLF1, BXLF2, BZLF1, and BZLF2. These results highlight the need to consider geographic variation in EBV genomes when devising strategies for exploiting adaptive immune responses against EBV-related cancers, ensuring greater global effectiveness and equity in prevention and treatment.

Identificación y evaluación de lesiones gástricas premalignas asociadas a la infección por Helicobacter pylori / Identification and evaluation of premalignant gastric lesions associated with Helicobacter pylori infection

Introducción: La infección por Helicobacter pylori es la causa principal de enfermedades gastroduodenales (gastritis crónica, úlceras pépticas y cáncer gástrico). En Guatemala existen pocos estudios sobre la prevalencia de H. pylori y su relación con enfermedades gastrointestinales, particularmente con cáncer. Objetivos: Identificar la presencia de lesiones premalignas (atrofia gástrica, metaplasia intestinal y displasia) y su relación con la infección por H. pylori en pacientes de consulta externa en unidades de gastroenterología de dos hospitales nacionales de la ciudad de Guatemala. Métodos: El diagnóstico histopatológico y bacteriológico se realizó por medio de las tinciones de H & E y Giemsa, cultivo e identificación bioquímica, detección de anticuerpos específicos mediante la prueba ELISA, diagnóstico molecular por la amplificación del gen glmM y genotipificación por PCR para identificar los genes VacA y CagA. Se analizaron datos clínico-epidemiológicos de los pacientes, la prevalencia de la infección por H. pylori y la genotipificación de la bacteria. Resultados: En 293 de los pacientes estudiados (83 por ciento) se encontró algún tipo de lesión premaligna; las más frecuentes fueron la atrofia gástrica (70 por ciento), metaplasia intestinal (11 por ciento) y displasia gástrica (2 por ciento). El 17 por ciento de los pacientes no presentó lesiones premalignas. Se halló una prevalencia de infección por H. pylori del 58 por ciento, y el gen cagA se detectó en 118 (57 por ciento) de los pacientes infectados. Conclusiones: La mayoría de los pacientes presentó atrofia gástrica (70 por ciento) y el 43,5 por ciento estaba infectado por H. pylori, principalmente con cepas CagA positivo. Este hecho confirma la importancia del estudio de H. pylori y su relación con cáncer gástrico(AU)

Introduction: Helicobacter pylori infection is the main cause of gastroduodenal diseases (chronic gastritis, peptic ulcer and gastric cancer). In Guatemala few studies have been carried out on the prevalence of H. pylori and its relationship with gastrointestinal diseases, particularly with cancer. Objective: To identify the presence of premalignant lesions (gastric atrophy, intestinal metaplasia and dysplasia) and their relationship with H. pylori infection in outpatients in gastroenterology units in two national hospitals in Guatemala City. Methods: Histopathological and bacteriological diagnostic testings were performed by H & E and Giemsa stain, culture and biochemical identification, detection of specific antibodies by ELISA, molecular diagnosis by glmM gene amplification, and genotypification by PCR to identify vacA and cagA genes. Clinical and epidemiological data from patients, prevalence of H. pylori infection, and bacterium genotypification were analyzed. Results: Among the studied patients, 293 (83 percent) presented some type of premalignant lesion. The most prevalent were gastric atrophy (70 percent), intestinal metaplasia (11 percent), and gastric dysplasia (2 percent). Seventeen percent of the patients did not have any premalignant lesions. The prevalence of H. pylori infection was 58 percent, and cagA gene was identified in 118 (57 percent) of the infected patients. Conclusions: The majority of the patients presented gastric atrophy (70 percent), and 43.5 percent were infected by H. pylori, mainly with positive cagA strains. This finding confirms the importance of studying H. pylori and its relationship with gastric cancer(AU)