Cancer is a group of genetic diseases characterized by the uncontrolled proliferation of heterogeneous cell populations with the ability to invade tissues locally and remotely from the site of origin (metastasis), responding to stimuli from the adjacent microenvironment and from the host organism. During oncogenesis, cancer not only escapes the host regulatory mechanisms, but also gains the ability to affect local and systemic homeostasis (1).

Cancer is the second leading cause of death worldwide; in 2022, 9,743,832 deaths were attributed to this disease, and it is estimated that the number of prevalent cases in 5 years will be 53,504,187 (2). Worldwide, GC is estimated to be the fifth most common cancer type in both sexes, ranking sixth for new cases, with 640,850 cases per year, and fourth in terms of mortality rate (GloboCan, 2020) (3).

The etiology of GC is complex, primarily due to genetic alterations and a set of factors (diet, lifestyle, genetics and socioeconomic factors). Significantly, 80% of cases are associated with infection with Helicobacter pylori (4,5).

Of note, <3% of GC cases are attributed to heredity causes, and these types of GC cancer cases include Hereditary GC (HGC), proximal polyposis of the stomach, and hereditary non-polyposis colorectal cancer (5). HGC is the best-known familial GC and is characterized by the loss of the CDH1 gene. Hereditary Diffuse GC (HDGC) is rare, with an incidence rate ranging from 0.3–3.1% in Korea and Japan. However, excluding the small portion of cases of familial GC syndrome, the risk of GC in those with a family history is three times higher vs. those with no history, which is higher than that for other adult solid cancer cases except ovarian cancer (6). Although family history is a systematically reported risk factor in GC, the molecular basis for familial clustering is unclear. Family members have shared exposure to carcinogens, (such as cigarette smoke and alcohol consumption), along with similar levels of hygiene, dietary habits (salty, spicy, and smoked foods), bacterial virulence, including Helicobacter pylori CagA⁺ and also genetic susceptibility (7).

Invasive GC is preceded by a long precancerous period, which can last for decades and thus provides ample opportunities to detect and treat precancerous lesions. When these lesions progress to an advanced stage, periodic endoscopic follow-ups should be performed to identify the lesions before they become invasive (8,9). Anatomic demarcations, histological differences, or both can be used to distinguish benign lesions from invasive lesions. Most relevant is the distinction between adenocarcinomas that arise from the cardia (the part of the stomach closest to the esophagus, cardia-GC) and other parts of the stomach (non-cardia-GC) (10). Currently, there are different histological classifications of GC, the most commonly used are the Lauren (11), Nakamura et al (12), Ming (8), Goseki et al (13), and the World Health Organization (WHO) classification systems (14).

GC can be divided into diffuse and intestinal GC based on its histological appearance as well as cardia and non-cardia-GC according to location. The epidemiological and molecular characteristics of GC differ according to the histological type and location of the tumor (6).

Intestinal-type GC (IGC) has well-defined structures or ductal chords surrounded by a zone of desmoplastic stroma. It forms adhesions or fibrous joint tissue within the tumor, with mixed inflammatory infiltration (15). IGC is observed more frequently in older adult patients and follows Correa's precancerous chain, which includes the following states: Atrophic gastritis, intestinal metaplasia and dysplasia (16). Tumor cells often have nuclei that are polymorphic and isochromatic with a coarse chromatin pattern; mitotic figures are thus easily detected. Intestinal-type carcinomas must be well or moderately differentiated, and diffuse-type adenocarcinomas have solitary or small groups of tumor cells without forming glandular structures (15).

Furthermore, Diffuse-type GC (DGC) occurs more frequently in younger patients, and there are no associations with atrophic gastritis or intestinal metaplasia (16). Clear cytoplasmic vacuoles may sometimes be observed. These cells that contain mucus push the nucleus to the periphery of the cell (signet ring cell carcinoma). The stroma formed is usually extensive, making it difficult to identify separate tumor cells on standard hematoxylin and eosin stains; additional keratin staining reveals the true extent of the tumor (15).

The pathogenicity of IGC has been well characterized and studied. However, diffuse GC (DGC) remains undefined, is considered genetically determined, and is less associated with environmental factors and the inflammatory cascade. Additionally, a minor proportion of DGC cases (1–3%) are inherently linked and associated with germline alterations in cell physiology, known as HDGC (7).

The stages of the precancerous cascade illustrated in Fig. 1 have been well characterized from the histopathological point of view. It is postulated that the progression from one stage to the next is determined by etiological factors linked to the inflammatory process and decades of progression (9). The stages of the precancerous cascade are non-atrophic gastritis, multifocal atrophic gastritis, complete intestinal metaplasia, incomplete intestinal metaplasia, dysplasia and adenocarcinoma (9).

Among the molecular pathogenesis, chromosome instability is involved (aneuploid, translocation, amplification, deletions and loss of heterozygosity), fusion genes, microsatellites instability (hypermethylation of promoters of DNA repair genes) and changes in gene expression profile (4,5,17).

In humans, the genome consists of 23 pairs of chromosomes [22 autosomes (44 chromosomes and one pair of sex chromosomes (XX or XY), for a total of 46 chromosomes] located in the nucleus, as well as a small chromosome in each mitochondrion. Each human chromosome has a short arm (‘p’ for ‘petit’) and a long arm (‘q’ for ‘queue’), separated by a centromere. The ends of chromosomes are called telomeres. Each chromosome arm is divided into regions, or cytogenetic bands, that can be observed using a microscope and special stains. The cytogenetic bands are labeled p1, p2, p3, q1, q2, q3, counting from the centromere to the telomeres. At higher resolutions, sub-bands can be identified within the bands. The sub-bands are also numbered from the centromere out toward the telomere. For example, the cytogenetic map location of the MYC gene is 8q24.21, which indicates it is located on chromosome 8, q arm, band 24, sub-band 21 and sub-sub-band 2. The ends of the chromosomes are labeled ptel and qtel. For example, the notation 8qtel refers to the end of the long arm of chromosome 8 (18).

CNA represent a genetic variation class involving cumulative somatic variations. CNA are defined as non-inherited genetic alterations in somatic cells (19). These unbalanced structural variants usually contain gains or losses. Their interpretation and the CNA report continue to be a topic of interest in health and disease and have an essential role in GC (19,20). The majority of gastric adenocarcinomas, similar to numerous other types of solid tumors, exhibit defects in the maintenance of genome stability, resulting in DNA CNA that may be analyzed using comparative genomic hybridization (21) and sequencing (22). Based on the aforementioned, it is a widespread phenomenon among humans, and several studies have focused on understanding these genomic alterations that are responsible for cancer. They may be used for its diagnosis and prognosis (23).

In the present review, CNA research on samples of patients with GC is discussed. In a previous investigation, it was noted that the 8q24 cytoband exhibited alterations (24), and thus this cytoband's role in this neoplasia is reviewed below. The complete sequence of chromosome 8 has 145,138,636 bases, the NCBI RefSeq access key corresponding to the GRCh38.p14 version of the human genome is NC_000008.11, the chromosome has 34 cytobands, 2,388 genes, and 4,651 proteins. Chromosome 8 has 103 genes related to cancer; 22 of these genes are in cytoband 8q24, and seven of these genes are reported to be associated with stomach cancer (25,26) (Table I; 27–49).

Alterations in the 8q24 cytoband have been associated with multiple conditions, including cancer; several mechanisms have been proposed, including chromosomal translocations (50), viral integration (51), identification of nucleotide variations (51–53), and variations in the number of copies (24). The 8q24.21 cytoband is one of the most studied due to its association with various types of cancer or complex diseases; this locus has very few protein-coding genes and is rich in long non-coding RNAs (lncRNAs) (54). The latter play a range of roles in transcription and translation; however, a number of the identified variants in these regions have been insufficiently studied. The study of this locus has presented several difficulties since most of the lncRNAs in 8q24.21 are not evolutionarily conserved, and there are no mouse orthologs (55).

Currently, repositories such as ENSEMBL (56) and UCSC (57) allow the consultation of different cytobands of the human genome in their different versions. Additionally, BioMart is a tool that provides an interface for accessing database collections, which allows annotating or obtaining genomics, genetics and proteomics records, amongst other tools. With the BioMart data mining tool (58), an analysis of 8q24 (GRCh38.p13) was performed; it has a length of 138.9 megabase pairs (Mbp) and seven segments, of which q24.3 is the longest (6.2 Mbp) and the one with the most significant number of coding genes, pseudogenes and small RNAs, and q24.11 is the smallest (1.6 Mbp) (Table II).

The 8q24 cytoband has 509 genes: 172 coding genes and 337 non-coding genes; among the non-coding ones, lncRNAs, microRNAs, miscellaneous RNAs, small nucleolar RNAs, small nuclear RNAs, and processed, unprocessed, polymorphic pseudogenes were identified (Table SI).

The most studied genes of this cytoband are those belonging to the MYC family (8q24.21: c-MYC, l-MYC, and n-MYC). The c-MYC proto-oncogene is affected in almost 20% of the different types of cancer, and it is suspected that it may be related to the functioning of other genes (59). It is a coding gene that participates in cell division and multiplication, maturation and apoptosis. To date, when searching for information on ‘8q24 cytoband AND cancer’ in PubMed (https://www.ncbi.nlm.nih.gov/pmc/), 248 articles were found (April 2023). When exploring the combination ‘8q24 cytoband AND GC’, 73 articles were found; however, when performing an advanced search (selecting the ‘Title and Abstract’ options) in PubMed with the combination ‘8q24 AND cancer’ a total of 1,553 articles were found, whereas when using ‘8q24 AND GC’ as the search term, only 50 articles were returned (Table SII). Based on these analyses, Fig. 2 was constructed, which serves as an axis for the following parts of the present review.

A total of three genes (pink rectangles) are demonstrated in Fig. 2: MYC, PVT1 and PTK2, which have been reported to be altered in GC (Table I), and nine genes (yellow rectangles) in which SNP alterations in GC have been described; the cytobands in which they were located were 8q24.13, 8q24.21 and 8q24.3. The information on all these cytobands can be found in Table SIII.

A total of seven genes related to GC are in cytoband 8q24 (ADGRB1, MTSS1, MYC, PSCA, PTK2, PTP4A3, and PVT1; Table I). The present bibliographic analysis determined the most frequently cited 12 genes (NSMCE2, PCAT1, CASC19, CASC8, CCAT2, PRNCR1, POU5F1B, PSCA, JRK, MYC, PVT1 and PTK2) (Table SIII). The genes that were present in both search strategies were MYC, PVT1, PTK2 and PSCA, and of these, the PSCA gene was the most cited in GC articles.

The PSCA gene has four SNPs: i) rs2978980, which is located at a functional enhancer in the 8q24.3 GC-susceptibility locus (60,61); ii) rs2294008, the T allele of which is a risk allele for diffuse-type GC (62); iii) rs2976392, which is associated with alterations in apoptosis/proliferation (63); iv) rs9297976, which can potentially be recommended as a criterion for identifying high-risk groups for the development of GC (64).

A SNP is a genomic variant at a single base position in DNA. Numerous studies have focused on identifying the mechanisms of specific SNPs in a genome on health, disease, drug responses, and other traits in SNPs can occur in promoters, exons, introns, untranslated regions (UTRs), amongst other regions; the molecular mechanisms that may be affected are described in Table III.

These alterations, as shown, affect the control of transcription and/or translation of the genes. These sequence changes can be insignificant or very relevant, affecting key molecules or ‘checkpoints’ of cellular homeostasis and leading to a predisposition to specific diseases such as various types of cancer, particularly in GC.

In the present review, 12 genes present in cytoband 8q24 related to GC (NSMCE2, PCAT1, CASC19, CASC8, CCAT2, PRNCR1, POU5F1B, PSCA, JRK, MYC, PVT1 and PTK2) are discussed. The PSCA gene was cited more frequently than others; it has four known SNPs associated with GC (rs2978980, rs2294008, rs2976392 and rs9297976). Thus, these SNPs should be further studied in different populations to determine their risk value in patients with GC.

Alterations in cytoband 8q24 can occur at the structural level (deletions, insertions and translocations, among other types), at the functional level (genes and proteins), and at the SNP level, which can translate to a risk of suffering from a disease depending on the base that is mutated, that is, if it occurs in an oncogene or tumor suppressor gene and the function of the affected gene. In GC, mutations in the PSCA gene and the presence of SNPs are consistent and are thus deserved of further study.