Linoleic acid is an omega-6 fatty acid abundant in common cooking oils such as corn oil and soybean oil. High linoleic oil consumption appears to increase breast cancer risk. However, the breast cancer connection is not straightforward since omega-6 fats are essential to health. In fact, the ratio of omega-6 to omega-3 fats in the diet appears to be more important than the absolute amounts.
Nevertheless, evidence is mounting that linoleic acid promotes breasts cancer development and metastasis directly. Now a new study has demonstrated how linoleic acid induces migration and invasion in triple negative (ER-/PR-/HER2-) breast cancer cells.
Omega-6 and omega-6 fatty acids
A low dietary omega-6 to omega-3 fatty acid ratio has been found to be associated with reduced breast cancer risk. While both omega-3 and omega-6 fats are necessary for health, the typical U.S. diet contains an abundance of omega-6 fatty acids, whereas consumers have to make a special effort to obtain omega-3s.
The omega-3 fatty acid alpha-linolenic acid found in plant-based foods such as walnuts is converted in the body to the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These are the omega-3 fats found in abundance in fatty fish that appear to protect against breast cancer. However, a high linoleic acid diet can interfere with the conversion of alpha-linolenic acid to EPA and DHA, according to a study performed in rats.
Sources of omega-3 and omega-6 polyunsaturated fatty acids (PUFAs)
While beneficial, the trend away from animal fats (such as lard) and partially hydrogenated oils in processed foods and fast food meals has left the false impression that high omega-6 fats such as soybean oil and corn oil are "healthy." Below are some dietary sources omega-3 fats that have also been reported to be associated with reduced breast cancer risk, as well as some common sources of omega-6 fats. Reducing consumption of omega-6 fats can be an important part of a strategy to improve your dietary omega-6 to omega-3 fat ratio.
The study referenced at the beginning of this news story was designed to investigate the mechanism of action by which linoleic acid induces migration of MDA-MB-231 triple negative breast cancer cells. Linoleic acid, an essential fatty acid which represents the major omega-6 polyunsaturated fatty acid in Western diets, can induce systemic inflammation, which contributes to chronic disease such as cancer. In breast cancer cells, linoleic acid has been shown to induce migration, one of the first necessary steps in metastasis. However, the signal transduction pathways involved in migration and whether linoleic acid induces invasion in triple negative breast cancer cells have not been determined. A signal transduction pathway is a set of chemical reactions within a cell that are triggered when a specified molecule attaches to a receptor on the cell membrane. Once cancer cells acquire the ability to migrate, or move, within their primary tumor, they must invade surrounding tissues or internal tumor vasculature to start the process of establishing a new tumor at a distant site.
- Arctic char
- Flaxseed & flaxseed oil
- Lake trout
- Salmon, wild
- Walnuts & walnut oil
In the study, the authors demonstrate that linoleic acid induces Akt2 activation, invasion, an increase in NFκB-DNA binding activity, miR34a upregulation and miR9 downregulation in triple negative breast cancer cells. Activation of the Akt gene is frequently observed in human cancer cells. The authors found that Akt2 activation requires EGFR and PI3K activity, but migration and invasion are dependent on FFAR4, EGFR and PI3K/Akt activity. The authors conclude that linoleic acid induces migration and invasion through an EGFR-/PI3K-/Akt-dependent pathway in triple negative breast cancer cells.
Please see our article on diet for triple negative patients for more information.
Selected breast cancer studies
Abstract 4536: Polyunsaturated fatty acids alter the epigenetic landscape in triple-negative breast cancer (TNBC)
Chattin AM, O’Brien M, Pardini RS. Abstract 4536: Polyunsaturated fatty acids alter the epigenetic landscape in triple-negative breast cancer (TNBC). Molecular and Cellular Biology, Genetics. American Association for Cancer Research; 2016; 10.1158/1538-7445.am2016-4536
Plasma Fatty Acid Ratios Affect Blood Gene Expression Profiles - A Cross-Sectional Study of the Norwegian Women and Cancer Post-Genome Cohort
Olsen KS, Fenton C, Frøyland L, Waaseth M, Paulssen RH, Lund E. Plasma Fatty Acid Ratios Affect Blood Gene Expression Profiles - A Cross-Sectional Study of the Norwegian Women and Cancer Post-Genome Cohort. PLoS ONE. Public Library of Science (PLoS); 2013; 8:e67270 10.1371/journal.pone.0067270
Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue
Pender-Cudlip MC, Krag KJ, Martini D, Yu J, Guidi A, Skinner SS, et al. Delta-6-desaturase activity and arachidonic acid synthesis are increased in human breast cancer tissue. Cancer Science. Wiley; 2013; 104:760-764 10.1111/cas.12129
The role of the tissue omega-6/omega-3 fatty acid ratio in regulating tumor angiogenesis
Kang JX, Liu A. The role of the tissue omega-6/omega-3 fatty acid ratio in regulating tumor angiogenesis. Cancer and Metastasis Reviews. Springer Science and Business Media LLC; 2012; 32:201-210 10.1007/s10555-012-9401-9
Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids
Gibson R, Neumann M, Lien E, Boyd K, Tu W. Docosahexaenoic acid synthesis from alpha-linolenic acid is inhibited by diets high in polyunsaturated fatty acids. Prostaglandins, Leukotrienes and Essential Fatty Acids. Elsevier BV; 2013; 88:139-146 10.1016/j.plefa.2012.04.003
Critical role of arachidonic acid-activated mTOR signaling in breast carcinogenesis and angiogenesis
Wen Z, Su Y, Lai P, Zhang Y, Xu Y, Zhao A, et al. Critical role of arachidonic acid-activated mTOR signaling in breast carcinogenesis and angiogenesis. Oncogene. Springer Science and Business Media LLC; 2012; 32:160-170 10.1038/onc.2012.47
Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A
Espinosa-Neira R, Mejia-Rangel J, Cortes-Reynosa P, Salazar EP. Linoleic acid induces an EMT-like process in mammary epithelial cells MCF10A. The International Journal of Biochemistry & Cell Biology. Elsevier BV; 2011; 43:1782-1791 10.1016/j.biocel.2011.08.017
Long-Chain n-3-to-n-6 Polyunsaturated Fatty Acid Ratios in Breast Adipose Tissue From Women With and Without Breast Cancer
Bagga D, Anders KH, Wang H, Glaspy JA. Long-Chain n-3-to-n-6 Polyunsaturated Fatty Acid Ratios in Breast Adipose Tissue From Women With and Without Breast Cancer. Nutrition and Cancer. Informa UK Limited; 2002; 42:180-185 10.1207/s15327914nc422_5