The Yang Laboratory has been heavily engaged in studying the effect of dietary sugar in breast cancer development and progression in preclinical settings. Sugar consumption has surged up to 100 pounds per person per year, and an increase in the consumption of added sugars, particularly sugar-sweetened beverages, has been identified as a pivotal contributor to worldwide epidemics of obesity, heart disease, and cancer. Their studies have suggested that refined sugar, especially sucrose, has the ability to stimulate the development of HER2 driven mouse mammary tumor, the human triple negative breast cancer MDA-231 xenograft tumor, and significantly increase lung metastasis of the mouse mammary gland 4T1 tumor model. Different from the “Warburg Effect”, the data generated in the Yang Laboratory suggested that the tumorigenic effect of sucrose was mediated by up-regulating 12-lipoxygenase (12-LOX) enzymes and its pro-inflammatory metabolite, 12-HETE, in all three breast cancer models tested. This certainly provided new insight as to how dietary sugar can potentially not only increase the risk of breast cancer, but also remarkably stimulate the development of metastasis. More importantly, they discovered for the first time that it is the fructose molecule within a sucrose enriched diet that leads to the significantly higher incidence of lung metastasis in the 4T1 mouse mammary gland tumor model. The importance of this study is highlighted by the fact the result of this study drew attention from over 240 news outlets around the world, including national news media NBC, Time, Today, Fox News, NPR etc. and 13 international media including UK (BBC), India, Argentina, Bangladesh etc. after their study on sugar promoting breast tumorigenesis was published in Cancer Research in January 2016.
In the News
The high amounts of dietary sugar in the typical Western diet may increase the risk of breast cancer and metastasis to the lungs, according to a study at The University of Texas MD Anderson Cancer Center.
The findings, published in the Jan. 1 online issue of Cancer Research,demonstrated dietary sugar’s effect on an enzymatic signaling pathway known as 12-LOX (12-lipoxygenase).
“We found that sucrose intake in mice comparable to levels of Western diets led to increased tumor growth and metastasis, when compared to a non-sugar starch diet,” said Peiying Yang, Ph.D., assistant professor of Palliative, Rehabilitation, and Integrative Medicine. “This was due, in part, to increased expression of 12-LOX and a related fatty acid called 12-HETE.”
Previous epidemiological studies have shown that dietary sugar intake has an impact on breast cancer development, with inflammation thought to play a role.
“The current study investigated the impact of dietary sugar on mammary gland tumor development in multiple mouse models, along with mechanisms that may be involved,” said co-author Lorenzo Cohen, Ph.D., professor of Palliative, Rehabilitation, and Integrative Medicine. “We determined that it was specifically fructose, in table sugar and high-fructose corn syrup, ubiquitous within our food system, which was responsible for facilitating lung metastasis and 12-HETE production in breast tumors.”
Cohen added that the data suggested that dietary sugar induces 12-LOX signaling to increase risks for breast cancer development and metastasis.
Identifying risk factors for breast cancer is a public health priority, say the authors. The researchers state that moderate sugar consumption is critical, given that the per capita consumption of sugar in the U.S. has surged to over 100 lbs. per year and an increase in consumption of sugar-sweetened beverages has been identified as a significant contributor to an epidemic of obesity, heart disease and cancer worldwide.
“Prior research has examined the role of sugar, especially glucose, and energy-based metabolic pathways in cancer development,” said Yang. “However, the inflammatory cascade may be an alternative route of studying sugar-driven carcinogenesis that warrants further study.”
No previous studies have investigated the direct effect of sugar consumption on the development of breast cancer using breast cancer animal models or examined specific mechanisms, she added.
The MD Anderson team conducted four different studies in which mice were randomized to different diet groups and fed one of four diets. At six months of age, 30 percent of mice on a starch-control diet had measurable tumors, whereas 50 to 58 percent of the mice on sucrose-enriched diets had developed mammary tumors. The study also showed that numbers of lung metastases were significantly higher in mice on a sucrose- or a fructose-enriched diet, versus mice on a starch-control diet.
“This study suggests that dietary sucrose or fructose induced 12-LOX and 12-HETE production in breast tumor cells in vivo,” said Cohen. “This indicates a possible signaling pathway responsible for sugar-promoted tumor growth in mice. How dietary sucrose and fructose induces 12-HETE and whether it has a direct or indirect effect remains in question.”
The study team believes that the mechanism by which dietary sucrose or fructose affects breast tumor growth and metastasis, especially through the 12-LOX pathways, warrants further investigation.
MD Anderson research team members included Yan Jiang, Yong Pan, Patrea Rhea, and Lin Tan, all of Palliative, Rehabilitation and Integrative Medicine; Mihai Gagea, D.V.M., Ph.D., Veterinary Medicine & Surgery; and Susan Fischer, Epigenetics & Molecular Carcinogenesis.
The study was funded by the National Institutes of Health (P30CA0166672), Mr. and Mrs. H. Leighton Steward and EOG Resources, Inc.
Study links high sugar intake to increased risk of breast cancer - Medical News Today
MD Anderson study links high sugar diets to breast cancer in mice - Houston Chronicle
Does consuming sugar increase my risk of developing breast cancer? - U.S. News & World Reports
Sugar boosts mammary tumor growth, metastasis in mice study - Cancer Network