Friday, August 1, 2014

The Tripping Point hypothesis in epigenetics - the start of cancer?

Researchers have long known that cancer is caused by damage to some critical stretch of DNA. Exposure to radiation as well as cigarette smoking causes genetic damage and that's how they cause cancer.

In recent times, the role of epigenetics, or more precisely, epigenetic damage as a cause of cancer has emerged as well.

So what is epigenetics? Some genes in our genome act as switches, turning other genes on or off. At embryonic stage, this switching on or off at different times and for different lengths of time is what determines which stem cells end up as eyes and which ones end up as our ears.

This switching on and off, does not end post the embryo stage or at birth, but is a constant and continuous process.

Whenever damage occurs in our body - to a tissue, a cell or even our genes, this switching kicks in to undertake necessary repair. Once the repair work is completed, the switch is reversed. If the damage occurs frequently or is intense, the number of times the switching occurs and the duration it is expressed is increased.

Now, for a moment, step aside into the mundane physical world. Consider a sudden burst of voltage in your home - what happens then? The circuit breaker will trip and the harmful burst of electricty will be cut off, till such time that an external influence (such as you or your electrician) does not fix and REVERSE it - the operative word being REVERSE.

It is from this analogy that i derive the name for the proposed hypothesis - The Tripping point.
Faced with a situation where the occurrence of damage is extremely frequent and extremely intense - such as that caused by chain smoking - how might epigenetics react? Is there a possibility that these switches are permanently forced in one state, just as the circuit breaker in our home example above? Does the process, coerced into producing cells to repair a damage, then simply not stop producing cells because it has reached the tripping point?


The hypothesis may have some substance after all. Seth Pollak, a professor at the University of Wisconsin and his team conducted a study on the impact that abuse during childhood may have at a cellular level.

It turns out that a gene NR3C1 that helps our body cope with stress is permanently switched off in most of the children who had undergone abuse during their childhood. When the body is exposed to stress, it releases the hormone cortisol that sends a signal to ramp up the blood sugar for a quick burst of energy at the expense of other energy demanding processes such as digestion, growth and immune functions. NR3C1 triggers a receptor that drains the cortisol from the body, allowing the body to return to its normal state after some time. If this gene is switched off, the body remains in "alert" mode all the time, which was the case with most of the children who participated in the study.

"They (the children) often misinterpret innocent behavior as threatening; they can be aggressive, and they struggle with change. The long-term results are the chronic psychological problems like anxiety and depression and chronic physical problems like heart disease and type II diabetes, which often surface years later in victims of childhood abuse", the study noted. In the context of my hypothesis, the tripping point for NR3C1 had been reached.

Is this then what occurs in certain types of cancers? Do some of us smoke to the point where the gene(s) that need(s) to repair the damage caused by smoking reaches the tripping point thus triggering the cancer itself?

From NOVA online
Abuse Casts a Long Shadow by Changing Children’s Genes
Epigenetic Therapy

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