An updated genetic and epigenetic aspects of Gallbladder Cancer

Gallbladder Cancer (GBC), is among the relatively rare but dangerous and malignant cancers that is most commonly seen in female. This cancer has a very high prevalence rate in parts of Asia and South America. Although the precise cause of gallbladder carcinogenesis is yet unknown, a number of risk factors and genetic abnormalities involving mutations or epigenetic modifications may be implicated. Epigenetic changes, such as methylation of tumor suppressor genes, histone acetylation of DNA repair genes, and micro RNA’s and long non-coding RNA’s modulation of cell division, proliferation and death, are linked to cancer development. GBC is influenced by various genetic factors, including gene mutations, single nucleotide polymorphisms (SNPs), Copy Number Variation (CNV), and genetic variations affecting inflammatory pathways, as well as hereditary syndromes. In recent years, research has focused on genetic and epigenetic factors affecting the occurrence and progression of GBC. Having a better understanding of these variables improves focused therapy development, early detection, and prognosis accuracy. Methods: Authentic scientific and literature databases including Pubmed, Scopus, MEDLINE, Embase, and Web of Science was used to collect information. Related keywords including GBC genetic and epigenetic, molecular mechanisms of GBC and related risk factors were used, and articles published in the last ۱۰ years (۲۰۱۴-۲۰۲۴) that dealt with these issues and the information obtained from them was collected and categorized, finally integrated and presented in the form of a review article. Results: In the pathogenesis of GBC, both genetic and epigenetic dysregulations have been observed, indicating their critical roles in the disease. Genetic alterations are pivotal in the development of GBC, with whole genome sequencing studies highlighting changes in key genes such as SMAD۴, K-RAS, and TP۵۳. These genetic changes are closely associated with GBC. SNPs are common genetic variations that can affect an individual's susceptibility to GBC. Notable SNPs linked to GBC include TNF-α (۳۰۸G>A) and IL-۶ (۱۷۴G>C). Epigenetic changes have been identified in GBC and if detected early in the course of the disease, may help in early diagnosis of the GBC resulting in improved prognoses. In this review, we collected the most important, most abundant and The most common variants and epigenetic factors that are related to GBC and play a role in the susceptibility to the disease ,prognosis and response to treatment. Conclusion: Genetic variants of predisposition genes consistently showed association across many analyses suggesting genetic variants and epigenetic changes of them are associated with GBC susceptibility and treatment outcomes. all the SNP’s and miRNA’s and lncRNA’s that collected here may be further assessed for their potential predictive and prognostic markers for GBC treatment performance. The progress of science and technology is an opportunity to expand research in this field and with a better and more accurate understanding of the pathophysiology mechanisms of the GBC and the identification of biomarkers, new ways to Early detection, new targeted treatments for patients and the spread of GBC will be reduced.

کلیدواژه ها:

Gallbladder Cancer genetic and epigenetic ، Gallbladder Cancer risk factors ، Genetic predisposion to Gallbladder Cancer ، Gallbladder Cancer prognosis