Saturday, January 7, 2012

Twins and Breast Cancer: Nature, Nurture, or Something Else?

Is our cancer the result of nature or nurture? Are we the victims of faulty DNA over which we have no control? Or of lifestyle and environmental factors that we can change? Or is there a third option?

Epigenetics is the study of that third option. This fairly new science covers the process by which nurture might affect nature. That is, things like diet and exercise might actually change the way our DNA influences our body. It’s a complex new field, and scientists are even having trouble defining it.

One way of illustrating it is through the lives of twins.

According to the theory of nature’s influence, we are formed by the genes we are born with—twins separated at birth grow up to live eerily similar lives, sharing marital history, criminal pasts, even athletic ability and sicknesses. The theory of the influence of nurture, however, maintains that our environment shapes us—our economic status, parental involvement, exposure to specific risks, diet, exercise, and so on.

Epigenetics, however, demonstrates that environmental factors can actually influence our genes, changing our genetic processes to make us more or less susceptible to disease. Some recent research on the influence of diet and exercise on the development of breast cancer demonstrates this epigenetic component.

Twins share the same DNA, which can make one more likely to have breast cancer if the other one is diagnosed with the disease.

Identical twins are formed from the same egg and begin in the womb with identical DNA; as the egg splits to become twins, the DNA likewise splits and does not necessarily divide equally, meaning that even identical twins do not have identical DNA. Fraternal twins develop from two different eggs and so they share DNA in the way all siblings do.
That’s the nature argument.

But not all twins share cancer—or any disease. It is common for one twin to get a serious illness that completely misses the other twin. This is the nurture argument—if twins share DNA but don’t share cancer, the environment has to have had some influence.

A discussion thread on twins with cancer explores this issue, with many respondents noting that they were diagnosed with breast cancer while their twin was not.
Why would one twin get breast cancer while another does not? National Geographic’s January 2012 issue has a cover story on epigenetics and twins, with some compelling stories that show how unpredictable disease can be even for people with shared DNA. And that unpredictability is one of the motivators for the study of epigenetics.

As National Geographic writer Peter Miller describes it:
If you think of our DNA as an immense piano keyboard and our genes as keys—each key symbolizing a segment of DNA responsible for a particular note, or trait, and all the keys combining to make us who we are—then epigenetic processes determine when and how each key can be struck, changing the tune being played.
One way the study of epigenetics is revolutionizing our understanding of biology is by revealing a mechanism by which the environment directly impacts genes. Studies of animals, for example, have shown that when a rat experiences stress during pregnancy, it can cause epigenetic changes in a fetus that lead to behavioral problems as the rodent grows up. Other epigenetic changes appear to occur randomly—throwing a monkey wrench into the engine of nature versus nurture. Still other epigenetic processes are normal, such as those that guide embryonic cells as they become heart, brain, or liver cells, for example.
Science Daily looked at why the same genetic mutation might affect people differently, using information from the Center for Genomic Regulation in Barcelona Spain. Citing research from the Center, published in the journal Nature, epigenetic researcher Alejandro Burga explains that identical cells do not exist:
In the last decade we have learned by studying very simple organisms such as bacteria that gene expression -- the extent to which a gene is turned on or off -- varies greatly among individuals, even in the absence of genetic and environmental variation. Two cells are not completely identical and sometimes these differences have their origin in random or stochastic processes.
So, while identical twins may appear identical, and while they as genetically close as two humans can be, they remain individuals on the cellular level. One may be more cancer-prone than the other even without differences in the environment.

So, what is it: Nature? Nurture? Both? Neither?

It seems to be a complex mix of all of the above, with our cancers as unique as we are.
Improving our diet and exercise certainly have been shown in multiple studies to reduce our risk of breast cancer. But sometimes the environmental risks that make one twin more prone to illness are no more under their control than their DNA. The way the fetuses develop in the womb, for example, might improve one twin's health while imperiling the other's. And sometimes, that tiny variation in DNA between twins makes all the difference in susceptibility to cancer.

Epigenetics, while not answering the question of what causes cancer, is absolutely getting us closer.

One basic genetic component in cancer is the BRCA genetic mutation, which runs in families; women with this mutation have between a 50 and 80 percent chance of breast cancer.

Women with triple-negative breast cancer are more likely to have the BRCA genetic mutation than those with other types of cancer.

So, do twins share a susceptibility to triple-negative breast cancer? Or is their tendency toward the disease the same as with other members of cancer-prone families?

In my initial search on this topic, I didn’t find hard research, but I did find some anecdotal evidence that might indicate that this question is worthy of study.

Fraternal twins Kim and Stephanie are both three years past a diagnosis of triple-negative breast cancer. They were adopted at birth and, through aggressive research, they learned that they shared a history of breast cancer with their biological mother, who died of the disease, which they suspect was also triple-negative. Both were diagnosed at 36 and are doing well, after double mastectomies.

And twins Kelly McSpirit Hanlon and Laura McSpirit Grier both have the BRCA genetic mutation and both were diagnosed with breast cancer in their 40s. Triple-negative disproportionately affects premenopausal women.

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Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

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