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How Spread of Cancer Is Related to Genetics

A new study based on melanoma, a type of cancer of the skin, has found that a single gene can alter the level of metastasis in this kind of cancer.
How Spread of Cancer Is Related to Genetics

Image Courtesy: Journal of Pineal Research

Cancer metastasis is a major cause of death which has attracted intense scientific research over the years. Metastasis is the process where cancer propagates to other tissues from where it started initially. It has long been thought that the genetic mutations which occur in the cells that cause cancer in them can also provide these cells with the ability to pervade other tissues further. But a question remains—does the inherited genetic make up of a person have a role in metastasis? 

Before proceeding further, let us quickly recapitulate some facts. In most cancers, the genetic mutation occurs in somatic cells. This means that these cancer-causing genetic mutations are not inherited. For a genetic mutation to be called inherited, the mutations must have occurred in the germ cells, that is the cells involved in reproduction. Precisely, the egg cells and the semen. 

The somatic mutations occur in a lifetime mostly due to external factors, like life style habits or environmental factors.

Apart from the somatic mutations, what the inherited mutations do in cancer metastasis has been a profound question in cancer research. Now, a Nature Medicine publication has come out with some elaborated data which indicate the link between cancer metastasis and someone’s inherited genetics. 

This study is based on melanoma, a type of cancer of the skin and finds that a single gene can alter the level of metastasis in this kind of cancer. The researchers also think that this gene and others can have similar effects in other cancer types. 

The specific gene in question is the APOE gene, which is present in all types of cells of the body. The production of the gene, a particular protein, appears to have interference in a number of processes that cancer cells undertake to metastasise. The important processes are like forming blood vessels, penetrating deep into other healthy tissues as well as resisting attacks of body’s cancer targeting immune cells. 

The APOE gene has three types, namely, ApoE2, ApoE3, ApoE4. An individual carries one type of the APOE gene among its varieties. It has been found that different melanoma patients have different degrees of progression of the cancer. The probable answer to it could be the presence of different APOE genes in different people. 

In the latest study, experiments with mice show that those possessing the ApoE4 variety of the gene have the smallest tumour and also the least spread of melanoma. Also, it was found that ApoE4 is the most effective version of the gene that could provide enhanced immune response to tumour cells. In comparison with other types of the APOE gene, mice having the ApoE4 type have higher amount of T cells involved in fighting melanoma tumour along with reduced blood vessels. Benjamin Ostendorf, the first author of the study says, We think that a major impact of the variations in ApoE arises from differences in how they modulate the immune system's attack.”

Recruiting genetic data from more than 300 melanoma patients also showed similar results as in the mice. Patients possessing the ApoE4 type could survive the longest and patients with ApoE2 type survived the least. While, the ApoE3 type’s ability to suppress tumour progression lies in between the other two. 

The genetic inheritance and its link to cancer progression is hoped to better development of cancer therapeutics in future.

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