Breast cancer is the most common cancer affecting women worldwide. For women living in low-risk countries, the risk of developing breast cancer increases upon migration to a high-risk country, suggesting a direct link with lifestyle, diet and environmental factors. Controversy still exists around the role of dietary fat in the promotion of breast cancer but specific lines of evidence suggest an important role for the omega-6 to omega-3 ratio on breast cancer risk . This ratio, which is easily modified by dietary manipulation, affects inflammation, immunity, tumour growth and survival and, not surprisingly, is gaining increasing interest for its impact as a management tool in aiding cancer survival.
The omega-6 and omega-3 ratio
Our hunter-gatherer ancestors consumed omega-6 and omega-3 fats in a ratio of roughly 1:1, but the last 100 years, and more rapidly so in the last few decades, has seen a marked shift in the ratio of omega-6 to omega-3 fats, with consumption of omega-6 fats increasing at the expense of omega-3 fats. The omega-6 to omega-3 fats ratio refers to the comparative amounts of each of these specific fatty acid groups in the diet, but it is the ratio of the specific fats arachidonic acid (AA) and eicosapentaenoic acid (EPA) that relate closely and accurately to health, with the AA to EPA ratio in blood plasma strongly correlated with breast cancer severity [2,3].
Mechanisms of action of AA and EPA in breast cancer
The long-chain omega-6 fatty acid AA is the precursor to products that drive inflammation and promote the proliferation, migration and invasiveness of cancer cells. In contrast, the long-chain omega-3 fatty acid EPA found in oily fish and fish oil reduces the production of these pro-inflammatory products by displacing AA from cell membranes, inhibiting the proliferation of cancerous cells and inducing apoptosis (programmed cell death) of cells carrying mutations that can lead to cancer. In addition, AA and EPA influence the activity of the tumour suppressor genes known as BRCA1 and BRCA2. As human ‘caretaker genes’, they produce proteins responsible for repairing DNA or destroying cells (if the DNA cannot be repaired). Mutations in BRCA1 and BRCA2 mean that damaged DNA is not repaired properly and this increases risks for breast cancer. AA is known to down regulate BRCA1 and BRCA2 expression, leading to less protein production, which, in turn, increases proliferation and uncontrolled growth of tumour cells. In contrast, EPA increases BRCA1 and BRCA2 expression, leading to higher protein production, a decrease in proliferation and an increase in programmed death of tumour cells .
Changing the AA to EPA ratio for favourable outcomes
Both the AA and EPA content of cell membranes can be altered through supplementation with fish oil and the subsequent increase in EPA levels results in a change in the production of pro-inflammatory and anti-inflammatory by-products, leading to changes in tumour cell growth. The average content of fish body oil is, however, only around 18% EPA, meaning that large volumes are needed to achieve the levels of EPA required for therapeutic outcomes. Indeed, several grams of EPA appear necessary to mediate inflammatory markers and influence breast cancer. Not surprisingly, highly purified ethyl E-EPA isolates are used routinely, rather than generic oils, in clinical nutrition studies where therapeutic doses are required. Indeed, pure E-EPA in doses of up to and around 4 grams can reduce the production of prostaglandin E2 and TNF-, IL-1, pro-inflammatory cytokines well documented for their key roles in driving tumour growth .
The past decade has seen a marked increase in the number of studies highlighting the modulation of the AA to EPA ratio as a potential treatment for a number of cancers, including breast cancer. Increasing EPA levels with purified EPA oil has consistently been shown to delay tumour appearance and decrease both the rate of growth and the size and number of tumours. In addition to having direct anticancer effects, EPA may be useful for the treatment of tamoxifen-resistant breast cancer cases , as an effective adjuvant to chemotherapy treatment, and may even help ameliorate some of the secondary complications associated with cancer .
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