Researchers have demonstrated that mammary tumor development can be directly inhibited by lifelong exposure to n-3 polyunsaturated fatty acid (PUFA) in mice. The study, published in the Journal of Nutritional Biochemistry, directly shows the anticancer activity of omega-3s. David Ma, PhD, associate professor at the University of Guelph and colleagues used an aggressive mouse breast cancer model that overexpressed HER2 to understand the long-term effect of omega-3s on breast cancer growth and development.
In a purely genetic approach to study the effect of omega-3 fatty acids on tumor development, the breast cancer model mice were crossed with mice harboring the fat-1 transgene to create a hybrid mouse model. The fat-1 transgene encodes for an enzyme that is able to endogenously convert n-6 PUFA to n-3 PUFA. The hybrid fat-1 breast cancer model mice had 30% smaller tumor volumes compared to their control counterparts that did not express the fat-1 gene. “Using this mouse model we show that it is the presence/absence of omega-3 fatty acids that was associated with tumor size and numbers,” said Ma.
In a different set of experiments using the breast cancer mouse model, mice were either fed a steady diet that included n-3 polyunsaturated fatty acids (n-3 PUFA) or same diet but without n-3 PUFA. The omega-3 fed mice also had 30% lower tumor volumes compared to the mice that ate a regular diet without n-3 PUFA.
Ma says that he did not anticipate a dramatic effect of the dietary fatty acid because the mouse model used develops breast cancer very aggressively. “I thought the aggressive nature of the cancer may overshadow any potential benefit of the omega-3s, but given that we are able to observe a benefit in this aggressive model, which is a HER2-positive breast cancer model, we have even greater confidence that the benefit is real,” said Ma. Using both a conventional diet and a genetic approach gave the researchers confidence that the omega-3s truly play a role in breast cancer prevention.
Both the genetically engineered and the mice fed an n-3 PUFA diet had similar numbers of tumors develop, about 3.5 per mouse compared to 5.5 tumors in control mice that neither harbored the fat-1 gene nor were exposed to n-3 PUFA in their diet. The reduction in number of tumors was statistically significant. No differences in the time to first detectable tumor were found for any of the mice.
The evidence that omega-3 fatty acids have a role in cancer prevention has been mixed. Direct causal effects from epidemiological studies linking dietary nutrients are difficult due to many confounding variables. For breast cancer, there have been inconsistent findings in humans on the effect of omega-3 fatty acids. Ma points out that these inconsistencies are mainly related to the challenging nature of nutrition research where careful consideration of lifelong dietary intake is needed but difficult to measure. Many confounding variables related to lifestyle and environment also contribute to equivocal results. “Teasing out the effect of one specific component from food and showing a cause-effect relationship is difficult,” said Ma,
To get around these challenges, the current research was essentially a nutrition experiment but using a modern genetic approach without having to manipulate the diet, said Ma.
Next Steps
“The present study examined the simple question of how lifelong exposure affects development,” said Ma. Ma and colleagues are now actively engaged in expanding their research to determine whether there is a critical window of mammary gland development that is most important for cancer prevention. Because the mammary glands develops during discrete periods in the womb, during puberty, and pregnancy/lactation, there may be critical times when environmental and biological factors play important roles in cancer development.
While Ma and colleagues are not working on studying the effect of omega-3 fatty acids on other cancer development, there is evidence that omega-3 fatty acids may help prevent colon and prostate cancers, as well as skin cancer. Ma would like this research to lead to more studies on how dietary components can reduce cancer risk and boost a healthier lifestyle. "I believe this study provides evidence that we should consider omega-3s as part of a healthy balanced diet to enhance the quality of our life and reduce the severity of cancer in those diagnosed with the disease.”
