The Epigenetics of Cholesterol, Smoking and Cancer

What this timely field of research tells us

Twisted cigarette

Our DNA is like an encyclopedia containing multiple volumes of genes. Certain genes are responsible for finding errors in these volumes and fixing them. When genes mutate, errors build up, and disease often follows.

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But what happens when the light we use to read the encyclopedia goes out? We can’t read in the dark.

That’s essentially what happens with “epigenetic” changes. The field of epigenetics deals with the way genes are expressed or activated, rather than mutations in the DNA we inherit from our parents. However, just like gene mutations, epigenetic alterations can lead to disease.

In this hot field of study, one of the most important topics is methylation. Think of methyl groups — groups of atoms that help control the way our genes function — as light switches in the metaphor above. In normal human development, they turn off and on at just the right time. For example, proper methylation leads to our developing hands and feet in the womb.

“You’d have a hard time finding anyone who doesn’t understand the dangers of cigarette smoke. But epigenetic research is showing us that smoking may be even riskier than we thought.”

Charis Eng, MD, PhD

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Founding Chairwoman of the Genomic Medicine Institute

But methylation can go wrong and increase our disease risk. Below are three examples of how this happens, and how research is responding.

Cholesterol and prostate cancer

When it comes to prostate cancer, the deadliest tumors are those that grow and spread rapidly. Interestingly, long-term statin use to control cholesterol has been shown to decrease the risk of the most aggressive tumor types. Because of this, doctors think too much cholesterol may play a part in how aggressive tumors are.

Angela Ting, PhD, of Cleveland Clinic’s Genomic Medicine Institute, is examining how this works through epigenetics. She and her colleagues focus on the ABCA1 gene. When this gene experiences too much methylation, cholesterol builds up. The research shows that this happens more often in aggressive tumor types.

Research is ongoing. However this work suggests not only that cholesterol matters in aggressive tumors, but also that we may be able to test for it to predict how aggressive tumors will be. Being able to predict tumor behavior would mean doctors could tailor prostate cancer treatments for better outcomes.

One more reason to stop smoking

You’d have a hard time finding anyone who doesn’t understand the dangers of cigarette smoke. But epigenetic research is showing us that smoking may be even riskier than we thought.

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Why? Because exposure to cigarette smoke seems to modify the methylation process in our bodies.

Research has examined the effects of exposure both before birth (through a mother’s smoking) and during adulthood. The results suggest smoking’s effects on methylation may help explain the link between this bad habit and cancer, plus other chronic diseases. If you need another reason to quit smoking, epigenetics may provide one.

Cowden Syndrome and cancer risk

My own lab specializes in the genes associated with Cowden Syndrome, an inherited syndrome that increases the risk for thyroid, breast and other types of cancer. 

Cowden Syndrome is usually tied to a mutation in the PTEN gene, but we’ve discovered it can have epigenetic causes, too. Certain people with Cowden Syndrome don’t have a PTEN mutation. Instead, they have abnormal methylation of the KLLN gene.

The difference matters. We’re still performing research, but we believe people with this KLLN methylation issue have an even higher lifetime breast cancer risk than the 85 percent that comes with a PTEN mutation. So when a person has a KLLN concern, careful monitoring and discussing options such as prophylactic mastectomy become even more important.

These are but a few examples among many being studied in labs across the country and around the world. Epigenetics is a young field, but we learn more about it with each passing year. We can use epigenetic markers to identify and manage disease. In the near future, we hope to be able to use them for life-saving treatments, too. 

Charis Eng, MD, PhD

Charis Eng, MD, PhD

Charis Eng, MD, PhD is founding chairwoman of the Genomic Medicine Institute and founding director of its Center for Personalized Genetic Healthcare. Dr. Eng is a global leader in cancer genetics and cancer genomic medicine.
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