Cancer causing mutations - 27 Nov

Cancer-causing mutations in blood stem cells may also link to heart disease

What causes heart diseases? We know that sometimes bad genes are responsible for it while sometimes unhealthy lifestyle is to be blamed for various heart conditions. But there is another factor that may take a toll on your heart as well. According to a latest research published in the New England Journal of Medicine, heart disease may also develop through a gradual accumulation of mutations in blood stem cells, just the way cancer forms in our body.

The study was, however, meant to detect how blood cancer could be traced early. Earlier studies proved that normal cells turn into cancerous cells in a slow process. It’s not an overnight affair. In case of blood cancer, scientists have found that blood cells go through a mutation that turns the normal cells into a pre-cancerous state. The moment the stem cells multiply, it creates a thread of clones of the blood stem cells, which causes the mutation and eventually leads to cancer.

The researchers at the Brigham and Women’s Hospital, the Broad Institute of Harvard and MIT tested the DNA sequences, derived from blood cells of more than 17,000 healthy people.  The team confirmed that they had found 160 genes that could be mutated in cancerous cells. The study further showed that the mutation is more common in people above 40. Also the frequency is higher in people above 40.

In the study, the team found that the mutation mainly takes place in 3 genes, namely DNMT3A, TET2, and ASXL1. The scientists have drawn a clear association between the mutation and higher risk of developing blood cancer. But they have also found another unexpected relation between the mutation and higher risk of death due other factors like heart disease. They have noticed that the heart diseases are one of the main reasons behind high mortality risk. Later studies have also confirmed the relation between gene mutation and heart diseases and also how heart diseases may worsen the situation for cancer patients.

The team collected stem cells from the bone marrow of mice and engineered them to have deficiency in Tet2. Tet2 is one of the 3 genes that are responsible for mutation when the risk of heart diseases is present. The bone marrow cells were injected into the mice that had higher cholesterol and all the symptoms of heart disease. They had noticed that the mice that were injected with cells sans Tet2 showed chances of heart diseases, compared to those who received normal bone barrow.

Dr. Sekar Kathiresan from the Broad Institute, one of the team leads, said, “We were fully expecting not to find anything here. But the odds of having an early heart attack are four-fold higher among younger people with CHIP mutations.”[1] He also felt that the results of the study have shown enough promise in therapies, as he said, “This is a totally different type of risk factor than hypertension or hypercholestserolemia [high blood cholesterol] or smoking. And since it’s a totally different risk factor that works through a different mechanism, it may lead to new treatment opportunities very different from the ones we have for heart disease at present.”2

Source:

http://www.nejm.org/doi/10.1056/NEJMoa1408617

http://time.com/4827232/cancer-mutations-heart-disease/

https://blog.cirm.ca.gov/2017/06/22/cancer-causing-mutations-in-blood-stem-cells-may-also-link-to-heart-disease/

[1] The Unexpected Way Genes Can Double Heart Disease Risk – By Alice Park June 21, 2017, TIME Health.

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