Sugar Consumption Could Mean Higher Breast Cancer Risk

The study,¹published inThe Journal of Cancer Research, stated that the average American consumes roughly 70 pounds of sugar per year, which could be increasing the risk of breast cancer. The authors attribute the effect to increased expression of 12-lipoxygenase (12-LOX) and its arachidonate metabolite 12-hydroxy-5Z,8Z,10E,14Z-eicosate-traenoic acid (12-HETE) in patients who consume more than sucrose than those who do not.

12-LOX and 12-HETE belong to a family on enzymes called lipoxygenases, which are currently known to play roles in tumorigenesis in both animal models and humans. The authors of the study state that 12-LOX proteins are commonly detected in multiple types of cancers and that 12-HETE has been shown to boost proliferation and invasion of breast cancer cells. Tissue 12-LOX protein expression was also heavily correlated with tumor node metastasis staging , which researchers in the study linked to possibly being a prognosis marker in breast cancer.

Research conducted on the mice consisted of four dietary intervention studies in three mouse models. These model groups included a mouse mammary gland tumor model carrying an MMTV/unactivate neu transgene as the control arm, one human triple-negative breast cancer (TNBC) cell orthotopic model, and a breast cancer lung metastasis model injected with 4T1 mouse breast cancer cells.

Researchers utilized multiple mice models to monitor tumor development and formulate a conclusion. The mice models used in the study were between 6 and 8 weeks old and were allowed to acclimatize for 72 hours prior to the start of the study. Mice were fed an AIN-76 rodent diet alongside water. The mice in the four studies were randomized to diet groups, where amounts of sucrose increased from 0 g/kg in the control arm to 62.5 g/kg, 125 g/kg, 250 g/kg, and 500 g/kg in the other arms daily.

At 6 months into the study, 30% of the mice carrying the MMTV/unactivate neu transgene had measurable tumors. This is in comparison to 50% of mice consuming 125 g/kg, 58% of mice consuming 250 g/kg, and 50% of mice consuming 500 g/kg in the sucrose-enriched diet. The study also states that mice in the 250 g/kg sucrose arm had tumors that weighed up to 50 mg heavier than those in the control arm. Mice consuming 500 g/kg of sucrose retained adenomas in their mammary glands as early as 3 months of age.

Mice injected with TNBC cells or 4T1 cells showed similar results. Mice with the 4T1 cells in the 250 g/kg sucrose group showed much heavier primary tumors and number of lung metastases than the control arm, with the former's tumors weighing around 784 mg and the latter's weighing roughly 389.4 mg (P<.05). Mice in the 4T1 cell group had an average of 16.7 nodules in their lungs, while the control arm showed only an average of 6.6 (P<.05). Mice with TNBC cells showed similar results.

"The data from the three breast carcinoma models consistently showed that sucrose-enriched diets compared with starch-based control diet, not only shortened the onset and increased proliferation of mammary gland tumors, but also notably increased the lung metastatic potential of mammary carcinoma," said Jiang et al, in the study. "Sugar has been linked to increased risk of cancer; however, such a link in breast cancer is still controversial. Our animal data supports the tumor-promoting effect of sugar in breast cancer development and metastasis."

The authors of the study state their intentions to continue the investigation into what role dietary fructose or fructose-containing sugar plays in breast tumorigenesis and metastasis, specifically through the 12-LOX pathway.

Reference

1. Jiang Y., Pan Y., Rhea P., et al, sucrose-enriched diet promotes tumorigenesis in mammary gland in part through the 12-Lipoxygenase Pathway.&nbsp;The Journal of Cancer Research. 2016;79:24-29.