Genetic basis of cancers

Dr Roopali Fotra
CANCER is one of the most common and severe diseases seen in the clinical medicine. It is a set of multiple disorders in which cells show abnormal proliferation leading to the formation of a mass or tumor known as Neoplasm.
A cancerous cell shares some common properties with that of a normal cell like cell division, migration and even invasion but what makes a cancer cell unique is the dysregulation and inappropriate expression of these attributes. Thirteen percent of the annual deaths worldwide are cancer-related and 70% of these are in the low- and middle-income countries. The increasing incidence and prevalence of malignant cancers year by year is a major issue of concern. Even in India, annual reported cases of cancers are also rising. According to ICMR- National Institute of Cancer Prevention and Research, more than 11,57,294 lacs new cancer cases are registered every year. In 2018, the total deaths cancer related deaths were about 7,84,821.
Cancer is often regarded as a multifactorial disorder which involves the influence of environment on our genes which when get affected lead to the onset and progression of disease. Various environmental factors like our lifestyle and dietary factors, consumption of alcohol and tobacco, exposure to viruses, harmful radiations, chemicals and toxins are considered to be the potential risk factors for cancer development. Recently, the role of Genetics in the development of cancer is being more widely recognized. With the advancements of genetic research and technologies, new possibilities have been explored for the screening, diagnosis, management and treatment of cancer.
Different types of Mutations are responsible for causing cancer which can occur either in somatic cells or germ cells. Depending upon the cell type so involved, cancer may be inherited, familial or sporadic. Inherited cancers are of dominant nature and can occur throughout every generation because of germ line mutations. Familial cancers also appear to run in the families but their inheritance pattern is different than inherited cancers because multiple genes are involved in cancer formation resulting in irregular occurrence. Sporadic cancers develop randomly in absence of any familial pattern.
Pioneering cytogenetic techniques have established that a cancerous cell undergoes a series of genetic alterations that get accumulated with the passage of time and are responsible for the development of cancer. In the course of carcinogenesis, cells experience several genetic alterations (including gains and deletions) that are associated with the transition from a preneoplastic lesion to an invasive tumor and finally to the metastatic state. The spectrum of cancer mutations is highly diverse. In some cases, there may be over expression of genes and in some instances, there may occur under expression of some important genes. A recent research study conducted by David Wishart has revealed that there are nearly 1000 known cancer associated genes in humans which are classified into: Oncogenes and Tumor Suppressor Genes. Oncogenes are the mutated version of normal cellular genes known as Proto-oncogenes. Proto-oncogenes normally participate in the regulation of cell proliferation and have the capacity to be upregulated therefore gain the potential for causing cancer. Amplification of a proto-oncogene through a vius is only one way to convert it into an Oncogene. In some cases, a proto-oncogene is also activated by a chromosomal mutation. The best known example is the translocation between chromosomes 9 and 22, commonly known as Philadelphia chromosome, which is known as a Biological Marker of Chronic Myeloid Leukemia.
Tumor suppressor genes (TSGs) as the name implies, block tumor development by regulating cellular growth and ensure genome stability under normal cellular conditions. Loss of function of proteins encoded by Tumor suppressor genes lead to uncontrolled cell division and abnormal cell growth. ABL1, ABL2, AKT2, BCL1, BCL2, BCL3, KRAS, KIT, CCND1, CCND2, EGFR, MYC, RET, TFG are some of the examples of Oncogenes. Tumor suppressor genes like RB1, TP53, APC, BRCA1, BRCA2, CDK6, FLT3, TNF, WT1, IL2, PTEN, PML NPM1, JAK2 are few examples to mention which suppress the cancer response in the body. The first TSG to be discovered was RB gene, absence of one functional copy of this gene could result in a rare form of eye tumor. Another very important gene is TP53, also known as “Guardian of genome because it plays a central role in controlling cell division and is known to be mutated in about 50% of human cancers.
The progress in our knowledge about gene mutations frequently occurring in cancers, combined with the development of modern molecular biology methods has led to both new diagnostic tools and new treatment modalities that have shown some success in the management of selected types of cancers.
At the end it can be stated that better understanding of the genetic basis of cancer onset and development makes it an important part of research and public health which no longer be overlooked. Thus, in addition to the routine cytological, histopathological or hematological analysis, we have one more option i.e. Availability of Genetic testing in different types of cancers that would give a clear picture about the virulence of the disease along with its inheritance pattern, risk of reoccurrence and management too. By coupling awareness of genetic aspects of cancer with a healthy lifestyle, we will be able to secure our genes very well thereby reducing the number of cancer cases significantly.
(The author is National Post Doc Fellow (NPDF), Science and Engineering Research Board (DST-SERB, Govt. of India)