Genetics and epigenetics of ovarian cancer

Introduction: Today, various factors play a role in the occurrence of cancer, and here we will examine the factors affecting the most common cause of death from ovarian cancer in women. In most cases, this disease appears in postmenopausal women with abdominal pain and distension for several months. We can say that only ۵ to ۱۰% of ovarian cancers are hereditary and most epigenetic factors control them so the disease rate is different in geographical areas and ethnic groups. Methods: This review article identified genetics and epigenetics mechanisms in the occurrence of ovarian cancer. The studies were conducted from the most recent full articles and irrelevant materials were removed. Results: In hereditary diseases, EOC patients carry pathogenic variants (PVs) in their genes. Epigenetics is another mechanism that causes disease by changing gene expression. Epigenetics includes types of DNA methylation, histone deacetylation, and miRNA expression, which play a role in the progression of HGSOC to chemical resistance. DNA methylation is mostly applied to cytosines and creates CpG islands, which are located in the regulatory region of genes. Reducing the methylation of CpG sites in promoter regions known as hypomethylation increases gene expression. The DNA strand is wrapped around ۴ histone proteins (H۳, H۴, H۲A, and H۲B) which create compact chromatin. Each of these proteins has a dense neutral chain with lysine and arginine residues. These chains are vulnerable to post-translational modifications such as removal or addition of acetyl groups. Histone deacetylase enzyme removes acetyl from histones, thereby increasing the electrostatic interactions between histones and DNA and restoring compact chromatin structure. The access to RNA polymerase is limited and gene expression is reduced. The expression of miRNAs is changed during cancer. Tumor suppressor miRNAs are usually downregulated and oncogenic miRNAs are overexpressed. This can occur due to epigenetic factors such as abnormal DNA methylation or histone changes. So, epigenetic changes affect gene expression and cannot change the DNA sequence. Conclusion: The process of cancer depends on various factors due to genetic and epigenetic changes in the cell. Recent research on malignant tumors has shown that according to the current situation, ۹۰% of malignant tumors are caused by external (carcinogenic) environmental factors. Diet, smoking, reproductive behavior, and alcohol consumption are involved in the development of ovarian, uterine, and breast cancers in women. During successive research about diet, no specific dietary factor is consistently and directly related to the risk of ovarian cancer, but a ۲۸% increase in ovarian cancer has been seen in women who constantly consume fat (fattening factors). Also, early menstruation and late menopause are known risk factors, while the use of oral contraceptives during pregnancy, breastfeeding, and tubal ligation or hysterectomy reduces the risk of ovarian cancer. By factoring in genetic factors such as mutations in BRCA and KRAS genes, hormone levels, and ovarian cancer stem cells that are inside the tumor, the risk of ovarian cancer can be greatly reduced by observing epigenetic factors.

کلیدواژه ها:

ovarian cancer ، epigenetics ، genetics ، gene expression