The diffuse-type gastric cancer epidemiology enigma

Abstract

Background: Intestinal and diffuse gastric adenocarcinomas differ in clinical, epidemiological and molecular features. However, most of the concepts related to the intestinal-type are translated to gastric adenocarcinoma in general; thus, the peculiarities of the diffuse-type are underappreciated. Results: Besides its growing importance, there are many gaps about the diffuse-type carcinogenesis and, as a result, its epidemiologic and pathogenetic features remain poorly understood. Conclusions: Alternative hypotheses to explain these features are discussed, including the role of the gastric microbiota, medical therapies, and modifications in the stomach's microenvironment. Background Gastric adenocarcinoma (GAC) is a leading cause of cancer-related deaths, although a reduction in incidence has been observed [1, 2]. Whereas these are different histology entities [3], intestinal and diffuse Lauren's GAC types are jointly considered when interpreting epidemiological data, and when contemplating interventional approaches aiming to reduce gastric cancer (GC) burden [1, 2]. Since the intestinal-GAC has been historically the most often studied type, data from this tumor are usually extrapolated to the diffuse-GAC. However, when examining and interpreting carcinogens and the epidemiology of diffuse-type carcinogenesis, inconsistences with regard to intestinal-type are evident [3]. These differences should be considered when trying to understand its specific pathogenesis and to apply this knowledge to develop interventional approaches. Our purpose in this commentary is to discuss some of the issues surrounding the diffuse-type GAC and to offer hypothesis to shed light on these features. Epidemiology GC was responsible for more than 1,000,000 new cases in 2018 with an estimated 783,000 deaths, being the fifth most frequent and the third leading cause of cancer death. The global incidence of GC varies markedly, with the highest burden observed in some of the less developed areas of the world. Asia, Eastern Europe and South America account for most GC cases and, thus, for their high mortality rates [1]. GAC is the most common type of GC, being classically classified, according to Lauren, as intestinal-or diffuse-types [2]. GAC incidence has been declining since 1930's [1], mainly due to the marked decrease of the intestinal-type. A decreasing trend of the intestinal-and a stable or increasing trend of the diffuse-type have been found in both high and low GC risk areas [4, 5]. However, the incidence in Korean Americans has declined during recent years, for both cardia and non-cardia sites and for both intestinal-and diffuse-type histology [6]. Several factors can explain the decreased incidence of GAC, including

Gastric Cancer Microbiome

“…There are few reports addressing microbiome differences among Lauren types. A need for augmentation of the number of analyzed cases, including full clinical information, may shed light on putative differences among histological, localization, and staging features [29].…”

Copy number alterations and epithelial-mesenchymal transition genes in diffuse and intestinal gastric cancers in Mexican patients

“…At present, the differences between DGC and IGC have been insufficiently explored and understood; differences in etiology, location, incidence, genetic profiles, among others, have been observed (52). The GC CNA-EMT network (Figure 5) was generated with relevant genes according to different criteria: frequency among patients as well as genetic connections, reported pathways, and experimental associations with several databases: EMTDB, The Human Protein Atlas, COSMIC (53), Cancer Hallmark Genes (CHG) database (54).…”

Gastric Microbiota beyond H. pylori: An Emerging Critical Character in Gastric Carcinogenesis

“…Additionally, epidemiological studies have shown the association of H. pylori abundance with different GC subtypes. For instance, the incidence of intestinal-type GC exhibits a markedly declining trend, whereas the diffuse type shows an increasing trend in both high-and low-risk areas for GC [49]. The decreased incidence of intestinal-type GC has been principally attributed to improved food preservation and declined H. pylori infection rates [1,4].…”