Introduction:
The urogenital system is one of the most important systems in the body. This system helps in both excretion of urine and the reproductive process. Also, accessory functions of reproduction are maintained by this system. Cancer of the urogenital system is very common in men and is considered one of the major causes of global mortality. The involvement of genetic factors in such cases can be helpful in understanding the prognosis of the diseases.
What Is Urological Cancer?
Urological cancers are a variety of cancerous conditions that include prostate, bladder, testis, and penis cancer.
Bladder Cancer:
Bladder cancer is the most common type of cancer of the urinary tract. It is the fourth most common cancer among men and the seventh most commonest cancer in the world. It is the sixth most common among men in the United States. The risk factors for bladder cancer are smoking, occupational exposure to the chemicals, carcinogenic chemicals, and schistosomiasis infection (infection caused by parasitic worms). Chemicals like arsenic, cyclophosphamide (a medicine used for the treatment of neoplasms), arylamine dye, and aniline dye are one of the causes. Exposure to substances like petroleum products, rubber, and paint is associated with such types of cancer. The bladder cancer can be of three types. 90 percent of cases of bladder cancer belong to urethral carcinoma. Other types are adenocarcinoma and squamous cell carcinoma of the urinary bladder. According to the mode of invasion, it can be non-invasive, non-muscle invasive, and muscle-invasive. The symptoms of bladder cancer are:
-
Presence of blood in the urine. Sometimes blood clots are present.
-
Pain during urination.
-
The increased urge to urinate but no urinary output.
-
Unilateral pain in the lower back region.
Prostate Cancer:
Prostate cancer is the most common cancer among men. It is the fifth leading cause of death in men worldwide. The incidence of prostate cancer is higher in developed countries. Changes in the glandular cells of the prostate glands are responsible for this carcinoma. Smoking, excessive alcohol consumption, sexually transmitted infections, and inflammation of the prostate gland are potential risks for developing prostate cancer. Mutation of BRCA1 and BRCA2 genes is related to the development of prostate cancer. Prostate cancer usually grows from the peripheral basal cells and gradually involves the whole prostate and tissues outside the prostate. Adenocarcinoma of the prostate is the most common type of prostate cancer. Other types of prostate cancer are squamous cell carcinoma of the prostate, transitional cell carcinoma, and small cell prostate cancer.
Testicular Cancer:
It is one of the common malignant conditions among young men. Infections from human papillomavirus (HPV), Epstein-Barr virus (EBV), cytomegalovirus (CMV), and genetic factors are associated with this type of cancer. Swelling in the testis and change in the consistency of the testis are usual signs and symptoms of this condition.
What Is the Role of Epigenetics in Urological Cancer?
Epigenetics is the change in the genetic activity of the cell caused by genetic alterations. The alterations are mainly three types. These are; DNA (deoxyribonucleic acid) methylation, microRNA (ribonucleic acid) modifications, and histone modification.
In DNA methylation, covalent bond formation occurs due to the addition of methyl groups to the carbon atom. This change in the DNA is responsible for the change in the CpG islands, which causes suppression of the tumor suppressor gene. DNA methyltransferase is the responsible enzyme for this process and carries it forward through subsequent cell divisions. Another abnormality related to DNA methylation is DNA hypomethylation. This process involves the removal of the methyl group from methylated DNA strands. This also increases the prevalence of urological cancer.
RNA interference plays a crucial role in genetic expression. MicroRNAs (miRNAs) regulate this process. Dysregulation of the miRNA is responsible for cellular proliferation and apoptosis changes. Thus overexpression of miRNA is considered oncogenic.
Histone is a type of protein molecule. Around this, DNA collides and forms the nucleosome. Each nucleosome is made up of eight histone protein molecules. These are; H2A, H2B, H3, and H4. Due to several mechanisms like methylation, acetylation, and phosphorylation, modification of histone structure takes place. This causes the silencing or activation of other genes. Two enzymes play a crucial role in this process. The addition of the acetyl group is carried out by histone acetyltransferases, and histone deacetylases catalyze its removal. The modifications made in histone proteins are H3K4me, H3K4me2, H3K4me3, and H3K9ac.
Diagnostic Role of Epigenetics:
-
Diagnosis of bladder cancer can be made through the use of epigenetic procedures. Detecting the presence of methylation in a gene through methylation-specific polymerase chain reaction (PCR) is helpful in detecting bladder cancer. Methylation in the SFRP1, IRF8, APC, and RASSF1A genes is suggestive of bladder cancer. Methylation associated with TET2, DNMT3B, IDH1, and BRAF are linked to prostate cancer. Hypermethylation of RASSF1A, BRCA1, APC, CDH1, and FHIT genes are responsible for testicular cancer.
-
MicroRNA-371, miRNA-372, and miRNA-373 are a group of miRNA genes that are located in chromosome number 19. This cluster of micro RNA is responsible for the self-renewal process of the cells. These microRNAs act as a biomarker for testicular cancer. MicroRNA-34a is responsible for the inhibition of epithelial-mesenchymal transition, which is associated with bladder cancer.
-
Dimethylation of subunits of the histone protein, such as H2A and H4R3, is related to testicular cancer. Histone acetylation, such as H3K27ac, is linked to prostate cancer.
Therapeutic Role of Epigenetics:
-
Inhibiting the action of epigenetic-modifying enzymes can be useful for restricting the progression of the disease. Inhibition of the action of histone acetyltransferases and histone deacetylases is related to the treatment of urological cancers. Drugs like Panobinostat, Romidepsin, Entinostat, and Mocetinostat act as histone deacetylases inhibitors by preventing its interaction with zinc.
-
Inhibitors of DNA methyltransferase prevent DNA methylation. Such drugs are divided into nucleoside analogs and non-nucleoside analogs. Drugs like Azacitidine and Decitabine belong to this group.
Conclusion:
Urological cancers are one of the most common types of cancer in the male. This is also associated with a high percentage of cancer-related deaths. Genetic factors are one of the most common causes of urological cancers. Genetic changes caused by processes like DNA methylation are related to cancer-related changes. Identification of such changes is important for diagnosing cancer. Also, epigenetic knowledge can be used for killing cancer cells.
