High cholesterol linked to increased breast cancer risk
MedWire News: Elevated cholesterol levels, typical of those in a Western-style diet, may accelerate the development of breast tumors and exacerbate their aggressiveness, US researchers report.
In future, drugs that target cholesterol metabolism, such as statins, could be used in addition to anti-tumor chemotherapy, say Frank and colleagues from Thomas Jefferson University, in Philadelphia, Pennsylvania.
The researchers note that breast cancer incidence is fives time higher in Western countries than in other developed countries. Moreover, migration from a region with low incidence to a region with high incidence increases breast cancer incidence in the immigrant population.
"These observations suggest a strong environmental influence on breast cancer development," says the team, who used a mouse model of mammary tumor formation (PyMTTg mice) to examine the role of cholesterol in the regulation of tumor progression.
From 4 weeks of age, the mice received either a Western-style diet that contained 20.20% fat and 0.20% cholesterol or normal chow that had only 4.50% fat and less than 0.03% cholesterol.
After 4 weeks, mice fed the cholesterol-rich diet had developed significantly more palpable tumors, than mice receiving normal chow, (1.9 versus 1.0 tumors per mouse). In addition, the tumors were approximately 1.5 times larger in mice on the cholesterol-rich diet compared with those on the normal diet (2.9 vs 4.2 g).
Furthermore, tumors were more aggressive - as indicated by raised levels of biochemical markers such as cyclin D1 - and tumor angiogenesis was enhanced in the mice that received the Western-style diet relative to those that had normal chow.
Finally, Frank and team observed a trend towards an increased number of lung metastases in mice fed the cholesterol-rich diet compared with those on the normal diet with a respective 33% and 23% developing more than 10 metastatic foci in the left lung.
When they examined cholesterol metabolism, the researchers found that the plasma cholesterol level in 12-week-old PyMTTg mice fed the cholesterol-rich diet was significantly lower (190.3 vs 205.7 mg/dl) than the level in age-matched wild-type mice fed the same diet.
This finding "may suggest that reduced plasma cholesterol is associated with enhanced cholesterol uptake by tumors," they write in the American Journal of Pathology.
"These data provide new evidence for an increase in cholesterol utilization by breast tumors and thus provides many new avenues for prevention, screening, and treatment," concluded Frank.
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By Laura Dean