Cancer Genetics and Epigenetics, 2025, Vol.13, No.2, 62-76 http://medscipublisher.com/index.php/cge 63 this study aims to point out the deficiencies of the current research cognition and provide suggestions for the subsequent research directions. Through these comprehensive analyses, this study hopes to provide new ideas for understanding the pathogenesis of EAC and promote the research and development of more advanced EAC treatment methods. 2 Epidemiological and Clinical Characteristics 2.1 The occurrence quantity and the number of patients with EAC In recent decades, in many Western countries, the occurrence frequency of esophageal adenocarcinoma (EAC) has increased significantly. Compared with women, this growth among men is particularly prominent (Coleman et al., 2017; Hoppe et al., 2021). Barrett's esophagus (BE) is a problem caused by changes in the inner cells of the esophagus due to long-term acid reflux disease (GERD), and it is the most significant precancerous lesion of EAC. Basically, all EAC cases evolve from BE, which indicates the importance of closely observing whether early signals of EAC occur in BE patients (Stachler et al., 2018; Hoppe et al., 2021). 2.2 Causes of disease and population characteristics Several factors leading to EAC have been discovered, among which GERD and BE are the most crucial. Obesity and smoking are also confirmed risk factors (Coleman et al., 2017; Hoppe et al., 2021). It is worth noting that drinking alcohol does not seem to increase the risk of EAC, but other lifestyle habits, such as exercise, diet and drug use, still require more research to determine their possible effects on the risk of EAC. Genetic susceptibility tendencies also have an impact, although their overall contribution to the risk of EAC is not significant (Coleman et al., 2017). The population characteristics of EAC patients are usually more male, and the proportion of patients with a Western background is higher (Coleman et al., 2017; Hoppe et al., 2021). 2.3 Disease manifestations and progression stages of EAC Because there are often no obvious symptoms in the early stage, EAC is usually discovered at a relatively late stage. Common manifestations include difficulty in eating, weight loss and chest pain. The development from BE to EAC goes through multiple steps. Initially, it is intestinal metaplasia, followed by mild abnormal hyperplasia, then severe abnormal hyperplasia, and finally adenocarcinoma is formed (Sundaram et al., 2022). The genetic composition of EAC is rather complex. Genes such as TP53, CDKN2A and KRAS often mutate (Stachler et al., 2018; Salem et al., 2018). This genetic complexity brings difficulties to the development of effective EAC-targeted therapies. This disease is often diagnosed late, seriously affecting the survival chance and treatment effect (Wang et al., 2015; Hoppe et al., 2021). EAC, especially in Western countries, is occurring more and more frequently, which emphasizes the need for better inspection and monitoring methods, particularly for high-risk groups with BE. Understanding the pathogenic causes and disease manifestations of EAC is of great significance for the early detection and effective response to this malignant disease. 3 Genetic and Molecular Alterations of EAC 3.1 Common gene mutations and their functions 3.1.1 TP53 mutation TP53 gene mutations are very common in esophageal adenocarcinoma (EAC), and approximately 70-80% of the tumors have this mutation (Hoppe et al., 2021). These mutations typically occur in the early stage of Barrett's esophagus (BE) developing into EAC, making genes unstable and activating carcinogenic processes (Sahgal et al., 2021). Patients with TP53 mutations have a poor response to preoperative treatment and a poor therapeutic effect. This indicates that this mutation may be used to distinguish different patients and formulate different treatment plans (Sihag et al., 2020). Moreover, studies have found that if there is TP53 mutation, the possibility of BE developing into severe abnormal hyperplasia or EAC is greater. Therefore, it is a key focus for early detection and intervention treatment (Stachler et al., 2018). 3.1.2 Loss of the CDKN2Agene The loss of the CDKN2A gene is also a common genetic alteration in EAC, and it usually occurs together with
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