Breast Cancer: The Sugar-Free-Strategy

8. March 2016
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Sugar is said to increase the risk of breast cancer and its metastasis in the lungs. The reason for this could be the increased formation of a fatty acid which increases inflammation in the body, according to an American research team. The relevant question now is: Hands off the sugar bowl?

The starting point is the formation of arachidonic acid. Animal organisms can either synthesise this themselves from the essential omega-6 fatty acid linoleic acid or they obtain it through diet. So-called cyclooxygenases (COX) metabolise arachidonic acid into various prostaglandins and thromboxanes. Those worthy of mention here include, for example, prostaglandin E2 (PGE2), which is among other things involved in the process of inflammation. However lipoxygenases (LOX) can also metabolise arachidonic acid into a number of products which promote and maintain inflammation. The LOXs are a family of cytosolic enzymes whose classification is defined according to the position of the hydroperoxy group (HOO-group). Three types have been differentiated in mammals: 5-lipoxygenase (5-LOX), 12-lipoxygenase (12-LOX) and 15-lipoxygenase (15-LOX).

LOX-concentration for the various isoforms is tissue dependent. Platelets for example contain only 12-LOX and can therefore only produce 12-hydroperoxyeicosatetraenoic acid (12-HPETE). Since 12-LOX as well as 5-LOX both occur in leukocytes, they can form both 5-HPETE as well as 12-HPETE. HPETEs are unstable and are among other things converted by peroxidases into their respective hydroxy fatty acids (HETE). The most common isoforms of the 12-LOX, according to the authors, are those of the platelet-type (12-LOX-P), the leukocyte type (12-LOX-L) and the epidermal type (12-LOX-E). The latter, however, has been found only in mice.

Sugar and the breast cancer

One study [Paywall] by Assistant Professor Peiying Yang and her group appeared in early January in the journal Cancer Research. For their investigations they used mice with a genetically increased risk of breast cancer. These were randomised at the age of five weeks into four groups and mice in each of these were fed with a different amount of sucrose (0 g/kg, 125 g/kg, 250 g/kg, 500 g/kg). Interestingly, the amount of consumption of sugar did not influence the body weight of the small rodents. At the age of six months 30 percent of the animals from the control group suffered measurable tumours. Where the sugar consumption was increased in the diet, this did not automatically lead to higher disease rates.

Whereas among the mice in the 125 g/kg sucrose group and 250 g/kg sucrose group 50 percent and 58 percent had the disease, the scientists were able to find among the animals that had received the most sucrose per kilogram a rate of “only” 50 percent measurable tumours. Further tests showed that the rodents from the 250 g/kg sucrose group compared with the control mice not only more frequently suffered breast cancer, but that the tumour tissue found was also on average heavier by 50 mg. The authors interpreted this as a sign that the sugar intake promotes both the origin of the cancer, and the proliferation of the breast cancer cells. Furthermore, the scientists found that, compared with the control group, the concentration of 12-LOX was elevated and that there was more than twice as much 12-HETE present (2,6). The scientists then examined the tissue of mice that had been fed with 500 g / kg sucrose. The little rodents already had adenomas in their mammary gland at the age of three months. Among the control mice, however, the researchers found only slight hyperplasia.

Hazardous fructose?

The American scientists then asked themselves the question as to who or what is precisely the root of all evil here: fructose or glucose?. This is because the disaccharide sucrose is known to consist of one molecule of glucose and one molecule fructose. It is decomposed into these components by special glucosidases. As part of another test the rodents therefore received a diet enriched either with sucrose (250 g/kg), glucose (125 g/kg), fructose (125 g/kg), or glucose and fructose (125 g/kg + 125 g/kg ). The result: compared with the mice that had consumed no sugar, the animals that had received fructose had both larger tumours and more metastases in their lungs (1.9 ± 0.4 per mouse in the saccharose group, 2.2 ± 0.4 per mouse in the fructose group, 2.6 ± 0.8 per mouse in fructose and glucose group vs. 0.4 ± 0.2 per mouse in the control group). The researchers did indeed find a significant increase in 12-HETE concentration only in the animals in the fructose and the fructose and glucose group.

A small retrospective look

The American scientists led by Assistant Professor Peiying Yang are not the first to assume a correlation between glucose and fructose, 12-LOX and 12-HETE concentration and (breast) cancer. Already 20 years ago an American Health Foundation research team [Paywall] observed that prostaglandin E2, 12-HETE and 15-HETE-values and cell invasion increased when cultured human breast cancer cells were cultivated in the presence of the omega-6 fatty acid linoleic acid. This cell invasion was able to be blocked by the addition of the 12-lipoxygenase inhibitor esculetin, but not by the selective cyclooxygenase inhibitor piroxicam.

In addition, when cultivating breast cancer cells in the presence of 12-HETE, the researchers found increased cell invasion; this however did not occur in the presence of 5-HETE or prostaglandin E2. The invasion was accompanied by increased enzymatic activity involving metalloprotease-9, a collagenase. In subsequent years, several studies have been published that dealt with the concentration of 12-LOX in breast cancer and its effects. Thus it should be possible, according to an Egyptian research team, based on the 12-LOX expression to make a statement as to how far the tumour has progressed.

In 2010 American scientists discovered that fructose causes the proliferation of pancreatic cancer cells [Paywall]. This stems from the fact that the metabolisation of fructose and glucose differ, they say. In addition fructose and its transporter GLUT5 are supposed to have a direct effect on tumour growth, for example on the breast cancer cells,

And now?

“Our results suggest that in mice in which 12-LOX/12-HETE production is stimulated by sugar or fructose in the diet, one potential pathway – particularly with view to tumour growth aided by sugar – exists in vivo in breast cancer cells”, the authors say. This study, according to the scientists, for the first time demonstrates a connection between sugar in the diet and breast cancer development and metastasis. It is however worth noting that neither sample size nor the raw data have been made available. In addition, it remains unclear how sucrose or fructose might boost 12-HETE production and whether this increase is due to direct or indirect effects. And finally, the results obtained merely present the scientists’ conceptual associations. The evidence that the increased production of 12-HETE and the tumour growth found actually relate to sugar intake still needs to be delivered. Based on this study therefore, no statement is able to be made about whether breast cancer patients or vulnerable women ought or ought not to stay away from sugar.

Original publication:

A Sucrose-EnrichedDietPromotestumorigenesis in Mammary Gland in Part throughthe 12-lipoxygenase Pathway
Peiying Yang et al.; Cancer Research, doi: 10.1158/0008-5472.CAN-14-3432; 2016

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Gynaecology, Medicine, Oncology

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