Approximately 90% of the world population is infected by Epstein-Barr virus (EBV). Usually, it infects B lymphocytes, predisposing them to malignant transformation. Infection of epithelial cells occurs rarely, and it is estimated that about to 10% of gastric cancer patients harbor EBV in their malignant cells. Given that gastric cancer is the third leading cause of cancerrelated mortality worldwide, with a global annual incidence of over 950,000 cases, EBV-positive gastric cancer is the largest group of EBV-associated malignancies. Based on gene expression profile studies, gastric cancer was recently categorized into four subtypes; EBV-positive, microsatellite unstable, genomically stable and chromosomal instability. Together with previous studies, this report provided a more detailed molecular characterization of gastric cancer, demonstrating that EBV-positive gastric cancer is a distinct molecular subtype of the disease, with unique genetic and epigenetic abnormalities, reflected in a specific phenotype. The recognition of characteristic molecular alterations in gastric cancer allows the identification of molecular pathways involved in cell proliferation and survival, with the potential to identify therapeutic targets. These findings highlight the enormous heterogeneity of gastric cancer, and the complex interplay between genetic and epigenetic alterations in the disease, and provide a roadmap to implementation of genome-guided personalized therapy in gastric cancer. The present review discusses the initial studies describing EBV-positive gastric cancer as a distinct clinical entity, presents recently described genetic and epigenetic alterations, and considers potential therapeutic insights derived from the recognition of this new molecular subtype of gastric adenocarcinoma.
Background: CRC incidence rates and human development index are demographically associated. It has been observed an increase of EOCRC incidence rates in the past years, predominantly reported by developed countries. However, such phenomenon is not well described globally, with unknown rates in low-and middle-income countries (LMIC), such as Brazil. We aim to evaluate the incidence rates and the clinicopathological features of EOCRC in a cancer center in Brazil.Methods: We retrospectively collected clinicopathological data from patients diagnosed with CRC in a Brazilian cancer center from January 2016 to December 2019. Two groups were categorized based on the age-of-onset of CRC: EOCRC (< 50 years) vs. Late-onset CRC (LOCRC) ( 50 years). The groups were compared for gender, TNM stage at presentation, body mass index (BMI), sidedness, RAS, BRAF, and microsatellite instability status (MSI) using Fisher's exact test and Mann-Whitney U test, and statistical significance assumed at p<0.05. The mean age-of-onset of CRC patients was compared among the years (2016 to 2019) by one-way ANOVA test.Results: A total of 388 patients were included, of which 76 (20%) were younger than 50 years. There was no statistically significant difference in the mean age-of-onset among the years 2016 to 2019 (p¼0.789) (Table ). The most common TNM stages were III (43% in EOCRC vs. 50% in LOCRC, p>0.05) and IV (36% vs. 27%, p>0.05). Leftsided tumors were represented by 74% vs. 64% (p¼0.147). Likewise, there was no statistically significant difference between the groups in relation to gender, BMI, RAS, BRAF and MSI status. Conclusions:In contrast to the data from developed countries, LMIC may present a distinct epidemiological trend of EOCRC, which strengths the hypothesis of the role of environmental factors as underlying causes of the rising incidence of EOCRC. Larger epidemiological study in Brazil is ongoing.Legal entity responsible for the study: Oncoclínicas.
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