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Cancer genetics: Beyond hereditary cancer

Agency | February 02, 2019 12:02 PM

The gene is a unit of inheritance of our DNA that determines our characteristics including physical, behavioural and clinical and the term 'hereditary' means passed from the genes of a parent to the child. In cancer genetics, often these terms are used interchangeably.

The majority of us have a perception of genetics in the terms of hereditary lineage. However, there are quite of few gene mutations which are not inherited but acquired during the course of individual's life due to a set of predisposing events or lifestyle habits.

This brings us to the question: "What can genetics do in cancer apart from telling the hereditary predisposition and vulnerability to cancer?" The answer is the D-P-T (Diagnosis-Prognosis-Therapeutics) Triangle.

For example: A 63-year-old man develops lung cancer without having any first/second degree relatives diagnosed with cancer. These are sporadic cancers constituting more than 85 per cent of all newly-diagnosed cancers. Scientific research has contributed significantly to our understanding of lung cancer, its onset and the importance of screening cancer-causing genes for mutations which helps physicians to provide targeted therapy to kill or overcome cancer.

The presence of EGFR gene mutation in lung cancer implies that one particular class of anti-cancer drugs are highly effective in killing lung cancer cells and thus improving the quality of life and survival of a patient. Beyond this, research identified a subsequent secondary mutation in the EGFR gene in patients who are already on targeted drug. These mutations make the cancer cells resistant to the drug.

To address this challenge, fourth generation drugs are in the pipeline that could specifically kill those cancer cells that have developed resistance to the first, second and third generation drugs. This is a classic example of how genetic testing has helped in treatment planning and management of the cancer and is an example of cancer genetics beyond heredity.

* Cancer genetics in diagnosis

An accurate diagnosis of a type or subtype of cancer can be helpful to better manage the disease. There are multiple other cases where mutation in genes confirm the diagnosis and hence guide the further course of action. For example, in leukemia, there are a set of genes, if mutated, that help in distinguishing myeloproliferative neoplasm (MPN - a type of leukemia) from other benign causes of cytopenias (reduction of mature blood cells).

* Cancer genetics in prognosis

Prognosis in simple terms mean prediction of how the disease is going to progress. This application is helpful to understand whether the disease requires aggressive treatment or not. For example: There is a standard recommendation of IGHV gene mutation testing in chronic lymphocytic leukemia. If this gene is mutated, clinical studies have shown that these patients do not show an aggressive disease phenotype and hence may not require aggressive treatment. However, for patients who are not mutated for the IGHV gene, clinical studies have shown that the disease progresses aggressively and the treatment regimen could be re-worked for improving the quality of life and survival of these patients.

* Cancer genetics in therapeutics

The term targeted therapy would not be the same in cancer, if not for genetics. There are some genes which help in treatment decision called oncogenes/tumor suppressors, wherein a sporadic mutation changes the function of the gene-inducing cellular processes leading to uncontrolled cell division causing cancer. This intrinsic property of the cancer cell is advantageous to drug manufacturers for developing molecules that block the protein and inhibit cancer progression or kill the cancer cells.

In India, the application of cancer genetic testing in therapeutic decisions has seen tremendous increase particularly in lung, breast, gastrointestinal and colorectal cancers.

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