Harnessing Nutrient Responsive Genes Against Breast Cancer

I am particularly interested in nutrient responsive genes, especially for altering the risk for and course of conditions such as breast cancer. Nutrient responsive genes, as their name implies, are those whose expression responds to their environment – specifically the nutrients we ingest. This effect is mediated via epigenetic alterations induced by those nutrients. This blog will explain how this relates to BRCA- and non-BRCA-related breast cancers, and how we can optimize our protection against breast cancer through epigenetically-targeted nutrients. Don’t miss the table at the end which lists specific nutrients that have been shown to alter gene expression relevant to breast cancer! As always, I look forward to your comments and feedback. – DrKF

The American Cancer Society estimates that a whopping 297,790 women and 2,800 men will be diagnosed with invasive breast cancer this year (2023) in the US alone. Other than spreading the word and engaging in Breast Cancer Awareness month activities, can we actually change these grim statistics?

Our opinion is – yes, if we look through the lens of epigenetics and biological aging. Cancers of all types can hijack our epigenetic machinery for their own end, like expert computer hackers. And, even if we do not have cancer present, as our biological (and chronological) age creeps higher, all-important tumor-suppressor genes (including the most famous, BRCA) and tumor repair genes can become hypermethylated and shut off. In addition, genes that promote cancer (called “oncogenes”) can become hypomethylated and turned on. Unfortunately, aging makes us epigenetically vulnerable to developing cancer, and cancer itself takes over our epigenetics.

Understanding these mechanisms, negative as they are, gives us an opportunity to address them. The promise of epigenetics is that our genes are NOT our destiny: There is much we can do – right now – to beneficially impact our epigenetic health. And knowing what those things are gives us an opportunity to positively influence our own health – and the health of future generations. In this blog we’ll explore how epigenetics, environment and our everyday choices (think lifestyle and nutrition) can influence cancer risk, healthspan and longevity.

 

What we know about BRCA gene mutations and breast cancer risk

Deriving its name from “breast cancer,” BRCA is a very important (and protective) tumor-suppressor gene. When it’s mutated, the likelihood of developing hormone-sensitive cancers rises exponentially. Indeed, if you have a BRCA1 or BRCA2 mutation, your lifetime risk of developing breast cancer is 82%. Which, I can certainly understand, feels like insurmountable odds, regardless of your health choices.

However, BRCA isn’t anywhere near the most common cause of breast cancer. In fact, only about 10% of breast cancer incidences are considered hereditary. And of those 10%, only about 25% are associated with mutations like BRCA1 or BRCA2.

Also, when you look into the history of the BRCA mutations and cancer risk, you find that before 1940, the risk of developing breast cancer was 24% with a BRCA1 or BRCA2 mutation, not 82%, as it is today. Clearly, something has changed. And that something is the environment, including toxic exposures, diet, and stress. Specifically, your environment affects your epigenetics, and your epigenetics then influences how your genes are expressed – whether toward or away from cancer.

Environmental influence on breast cancer risk, both BRCA- and non-BRCA-associated 

Dr. Mary-Claire 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 – all things that have been on the rise since the 1940s. 

However, you don’t need to be born with a BRCA1 or BRCA2 mutation to have this gene contribute to your risk of cancer. Even genes without mutations can be inappropriately methylated, and therefore act like a mutated gene without actually being mutated. For example, a number of studies show that the all-important BRCA1 and BRCA2 genes can be hypermethylated and therefore shut off. Science has also shown that mothers can pass on a hypermethylated BRCA1 gene to their daughters.

Targeting epigenetic health to reduce pro-cancer activity

Once you have cancer, we know that it hijacks epigenetic machinery for its own aims (namely, uncontrolled growth). Tests of the DNA methylation patterns present in breast cancer tumor cells shows that tumors are older, epigenetically, than the surrounding, normal tissue. Specifically, genes that inhibit the cancer are turned off, and genes that allow cancer to grow unchecked are on – which, unfortunately, is the same pattern we see in aging in general. 

This is all to say it needn’t be a BRCA1 or BRCA2 gene mutation that increases your risk of cancer. In fact, more likely, it’s your epigenetics, and how it is affecting whether those genes are turned on or turned off. As I explained above, the typical pattern associated with cancer is hypermethylation of tumor-suppressor genes, which essentially turns those all-important protector genes off. The trick, then, is to reverse that hypermethylation via demethylation. 

There are pharmaceutical demethylating drugs that can serve this purpose, but so far, most of them demethylate indiscriminately, and can have much broader (and therefore often harmful) effects than simply turning tumor-suppressor genes back on. Also, we have such a strong, safe option available to us, and that is consuming ample amounts of epinutrients. These polyphenolic compounds appear to be super important for keeping the BRCA genes well functioning: Two in vitro studies have indicate that exposure to toxins may contribute to the silencing of BRCA1 via hypermethylation, and that resveratrol – the antioxidant present in red and purple grapes, blueberries, cranberries, and more – reverses the effect. Other studies suggest that, in addition to resveratrol, the flavanols EGCG (from green tea) and genistein (from soy) also reverse hypermethylation of BRCA1. 

Another component of soy is the isoflavone daidzein, which is transformed by your gut microbes into equol. And equol has been shown to not only demethylate BRCA1 and BRCA2 genes, and thus promote re-expression of these genes, but also upregulate production of the all-important protective proteins that the BRCA1 and BRCA2 genes code for. In other in vitro studies, quercetin and curcumin together epigenetically enhanced BRCA1 expression via multiple mechanisms. These effective phytochemicals are all parts of the Younger You program.

In addition, every one of us has a lot of other tumor-suppressor genes. Luckily, many of them, including BRCA 1 or 2, have been shown to have their genetic expression favorably altered by certain epinutrients; I call any gene for which this is true a “nutrient-responsive gene”. 

 

Nutrient-responsive tumor-suppressor genes 

When it comes to preventing and treating cancer, tending to epigenetics and DNA methylation using the Younger You approach is likely to be an important strategy, as changes in DNA methylation underlie cancer initiation, promotion, and progression, particularly on tumor-suppressor genes (TSG), which are frequently hypermethylated (and thus turned off) in cancer. 

Below are some of the nutrient-responsive tumor-suppressor genes and the specific epinutrients that have been shown in in vitro studies to help balance their expression. Many of these epinutrients have long histories of being used by traditional systems of medicine for a broad array of uses, including reducing inflammation, providing antioxidant support, and treating conditions including cancer, heart disease, and allergies. 

The way they exert their influence in such a broad range of conditions is in part due to their ability to fine tune DNA methylation and augment epigenetic expression. Naturally, I support following the Younger You program as I think it’s the most comprehensive and upstream approach to fostering healthy DNA methylation patterns on your nutrient-responsive genes.

However, if you’ve gotten genetic or epigenetic testing results that show that you have a mutation, a single nucleotide polymorphism (SNP), or imbalanced DNA methylation on any of these genes, you can (in addition to any other recommended interventions) focus on prioritizing the epinutrients that have been shown by research to support that particular gene’s expression.

 

Nutrient-responsive gene	Epinutrients that may improve expression
BRCA1 and 2 (Breast Cancer Gene 1 and Breast Cancer Gene 2)	Resveratrol  EGCG  Curcumin  Quercetin  Genistein  Daidzein / equol  Sulforaphane  Kaempferol
GSTP1 (Glutathione S Transferase P1)	EGCG Ellagic acid Lycopene  Curcumin Genistein  Daidzein / equol  Myricetin  Hesperidin  Apigenin
TET1 and 2 (Ten-eleven translocation enzymes)	Vitamin C  Vitamin A  Vitamin D  Alpha ketoglutarate  Sulforaphane

 

There are several other nutrient-responsive genes, including NRF2 and MGMT, that play an important role in cancer prevention. You can find them (and the food sources of the epinutrients which influence these genes) in the Younger You book.

The take home message is that our environment, nutrition and lifestyle, via their effects on our epigenome, can have a much bigger impact on cancer risk (and health in general) than our genes. And even if you have a BRCA 1 or 2 genetic mutation, you can support your other nutrient-responsive tumor-suppressor genes by taking care of your epigenetics with targeted nutrition and lifestyle practices such as the Younger You approach. 

 

This blog was adapted from YOUNGER YOU by Dr. Kara Fitzgerald, courtesy of Hachette Book Group