Dr Amit Verma, Molecular Oncologist & Cancer Geneticist – Dr AV Cancer Institute of Personalized Cancer Therapy and Research, Gurgaon explains the genetics of cancer
The underlying mechanism of the transformation of a normal cell into a cancerous cell lies in the acquisition of faults in the genes. This is why cancer is called a genetic disease. The faults in the genes can be acquired (multifactorial) resulting in sporadic cancer or can be inherited from the parents called hereditary cancers. Body has a mechanism to repair these faulty genes (DNA repair mechanisms), which prevents the development of cancer. Exposure to various carcinogenic factors followed by failure to repair the abnormalities lead to the accumulation of the alterations in the genes (genetic mutations) which on the subsequent cell division cycles results in fast growth of the cells leading to cancer. This phenomenon is observed in all multiplying cells of the body with higher probability of cancer observed in those cells which are either highly exposed to the carcinogens (like lung epithelium exposed to tobacco) or are multiplying faster (like colon epithelium) leads to lung and colon cancer, respectively.
Most of the sporadic cancers are preventable (up to 50 per cent) just by avoiding the exposure. Still, as we grow old the multiplying cells eventually fail to repair the genetic alteration(s) that is why cancer is considered to be the disease of ageing. On the other hand, inherited genetic alterations that are passed on from one generation to the next put you at a higher risk of developing cancer and cannot be corrected. Inheriting a cancer-related genetic change doesn’t mean you will definitely get cancer. Reason being, every gene has 2 copies (one from mother and other from father), the normal gene prevents the cancer probability over the abnormal gene. But sometimes if the normal gene becomes abnormal it can increase the risk of developing cancer.
There is a scenario where the genes abnormality is not observed still the functions of the genes are altered (based on the altered expression of the genes), this is called epigenetic modification. These changes are not considered to be permanent and are reversible. This phenomenon supports the cancer growth.
There are technologies to understand the genetic and epigenetic alternations in normal and abnormal cells which helps us to understand the underlying mechanism of cancerous transformation. These technologies are not only limited to studying the genes (at DNA level) but their effect as well i.e., RNA and protein level. The common technologies used are Polymerase Chain Reaction (ARMS, methylation specific PCR), Sequencing (NGS and sanger), Fluorescence In Situ Hybridisation (FISH), Microarray, Karyotyping for the purpose of identification of four classes of genetic alterations i.e., Single Nucleotide Variations (SNV), insertions and deletions, Copy Number Variations (CNV), translocations. Identifying and understanding the genetic variations and hence, the mechanisms help to find out the reason for cancer as well as find out the treatment options based on these alterations (targeted therapies). This is called precision oncology or personalised cancer medicine. Further, if an individual is carrying abnormal genes, they can pass on to the next generation. The carriers in next generation can be identified through genetic testing and can be put on various cancer preventive strategies. Undertaking the test can be a complex personal decision made for different reasons but best made after talking with your family, experts like molecular oncologist, cancer geneticist, and genetic counsellor.
Genetic counsellors, who guide the individuals, play a very important role in the process to make it smooth and easy. The testing process has multiple stages that include the risk assessment to find out the personal and family history, pre-test genetic counselling to discuss the risk of developing cancer, pros and cons of genetic testing and potential implications. Thereafter, informed consent is taken and specimen gets sent for testing. After the results are received from the laboratory, post-test genetic counselling is carried out to discuss results and further management.
This is an evolving science and genetic alterations found on this date may have different outcomes in future which requires deep understanding. To know more about the testing, its implications and limitations, get in touch with the experts!
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