BRCA Mutations, Breast Cancer, and Epigenetics: Is the Risk Modifiable?
It’s been a busy, productive and rather amazing Fall. Lots to write about. In celebration of the gorgeous New England weather, I’ve been spending much time on my bike the last couple of months, and it feels great!
Riding on Ridgefield back roads. Nothing beats it.
I just returned from speaking at the Nutri Advanced conference in London where Drs. Jeff Bland, Andrea Girman and Joe Pizzorno also presented. It was a great conference—the largest yet. UK is embracing Functional Medicine. And London was also absolutely lovely the week I was there.
The Millennium bridge, crossing the Thames from St. Paul’s to the Tate Modern. With Dr. Andrea Girman. We just saw the play Light Princess- words and music by Tori Amos. Amazing!
As always, I was thrilled to hear Dr. Bland speak. A founding father of Functional Medicine (he coined the term), his words nourish intellectually and also spiritually. Listening to him feels like receiving transmission from a Zen master who happens to have a PhD in nutritional biochemistry.
Jeff presented on epigenetics, that is, the way in which environment can shape our DNA expression and determine whether or not we get a particular disease.
So, just because you have the DNA associated with a particular disease doesn’t mean you’re getting the disease. This is such an empowering statement. I’ll say it again: Just because you have the DNA, doesn’t mean you’re getting the disease.
Jeff provided a potent example of this truth: The BRCA1 and BRCA2 mutations are very closely associated with breast and ovarian cancer. Indeed, if you have a BRCA mutation, your lifetime risk of developing breast cancer is greater than 80%. Recall that Angelina Jolie—who has the BRCA1 mutation–just had a double mastectomy to significantly reduce her risk of developing breast cancer.
If you have a BRCA mutation, it seems that you’re going to get cancer, regardless of your health choices, doesn’t it? I certainly admire Angelina’s courage to reduce her risk.
However, if we look into the history of the BRCA mutations and cancer risk, we find that [in a study of women born] before 1940, the risk was 24% with the BRCA mutation, not 82%, as it is today. Clearly, environment is playing a big role in the development of breast cancer even with the BRCA mutations.
What’s going on?
Dr. Mary King, the scientist who discovered the BRCA mutations, recognized the environmental influence on cancer risk. She specifically cited adolescent obesity, lack of exercise and early age of menarche as factors in the rise of BRCA-associated cancers.
I began thinking about the BRCA mutations and environmental influence in 2007 when I was working at Metametrix Laboratory. My attention was on the influence of fatty acids on hormone-sensitive cancers. A big question for me was: What does a functioning BRCA protein do in the body? As I was drilling down into the literature, I made a fascinating discovery that I rarely see discussed. This discovery gave me a clear treatment direction on how we might reduce risk for individuals with the BRCA mutation.
What does a normally functioning BRCA protein do in the body?
Functioning BRCA proteins are huge, complex structures involved in a good deal of regulatory activity in the body. They are recognized as tumor suppressor genes; they repair DNA.
A lesser recognized BRCA1 role has to do with its ability to potently down-regulate (inhibit) the body’s production of the enzyme aromatase.
What does aromatase do in the body, and why do we want to inhibit it?
Aromatase is the enzyme involved in making estrogen. And in this particular context, estrogen promotes cancers like breast and ovarian. You’ve likely heard of aromatase inhibitors — drugs that are commonly used to treat these cancers. (Note that estrogen has many essential, healthy, anti-inflammatory roles as well; but that’s for another discussion.)
Not surprisingly, if you look at aromatase in those with the BRCA1 mutation, it’s a lot higher than it should be. So there’s a lot more estrogen than there should be — hence the cancer risk.
Back to the fatty acid story.
When I discovered the BRCA1/aromatase link, I also learned that the pro-inflammatory fatty acid, called arachidonic acid, makes a compound called PGE2. PGE2 inhibits the good deeds of a normal BRCA1 and promotes aggressive aromatase expression. This results in lots of estrogen production and increased breast and ovarian cancer risk.
In other words, PGE2, from arachidonic acid, can behave like a BRCA1 mutation.
Arachidonic acid (AA) is an omega 6 fatty acid. Some AA is essential for a normal immune response; but anyone eating a typical diabetogenic diet — nutrient-void, too much sugar, simple carb and inflammatory omega 6 fats — is making way too much arachidonic acid (and therefore PGE2). Globally — not just in the West — most of us eat this unhealthy diet.
Therefore, one of the most fundamental ways we combat breast and ovarian cancer is by eating a healthy, anti-inflammatory diet. Those with the BRCA mutation? All the more necessary, even urgent, is the anti-inflammatory diet.
Returning to Dr. King’s observations, everything that she suggests will reduce excess or toxic estrogen exposures: More exercise, less obesity (starting early), better diets, later menarche. And of course, all of these are known to reduce cancer risk. (Early menarche is influenced by early estrogen exposures. Therefore, if you want to influence your daughter’s menarche, these changes should be made even before you conceive her, but certainly in early childhood.)
I want this blog to feel empowering for those with the BRCA mutations, or those concerned about hormone-sensitive cancers. The reality is there is much we can do to minimize the impact of estrogens on the body. Any good integrative doctor can come up with a robust to-do list. The fact is, many, many botanicals can interfere with the production of PGE2. If we pack our body full of the good omega 3 fatty acids, also, we will inhibit PGE2 availability. And as I mentioned, perhaps the most powerful factor is an anti-inflammatory eating plan.
Here are just a few of my anti-inflammatory/estrogen modulating/cancer-protective favorites:
- -High dose omega 3 fatty acids
- -Reduce stress (stress > inflammation > PGE2 > aromatase > estrogen)
- -Resolve insulin resistance (high insulin increases arachidonic acid, which will ultimately increase estrogen)
- -Avoid toxins such as BPA, pesticides, herbicides, parabens, phthalates, etc. All have an estrogenic effect and will contribute to the estrogen pool.
- -Eat organic or clean as much as possible
– See more at: http://www.drkarafitzgerald.com/brca-mutations#sthash.sx0tRdRy.dpuf