Just like smoking, obesity has been in the bad light for being one of the risk factors for several diseases including cancer. However, the exact link and mechanism has not been well understood till two teams of researchers under the leadership of Donald McDonnell at Duke and Philip Shaul of University of Texas explored to find out the role of 27-hydroxycholesterol in spurting cancer growth. Their research has revealed the effect of 27-hydroxy cholesterol to be similar to that of estrogen in promoting cancer growth.
The finding is crucial since a low fat diet with less cholesterol can thus lessen the risk of cancer. The role of estrogen in promoting the cancer growth especially in breast cancer has been previously established. The fat tissue has also been proved to promote the production of estrogen. The current research has revealed a completely different mechanism involving the cholesterol directly (27 HC is one of the cholesterol metabolite) which function exactly like estrogen in promoting the cancer growth.
In women past the menopause, the risk should be significantly lower due to the absence of estrogen production. However, this new method of alleviating the risk of cancer through cholesterol seems to be a plausible explanation for the prevalence of breast cancer even in menopausal women.
In the finding published in the journal science, it is reported that human breast cancer cells were found to grow faster in vitro conditions when 27 Hydroxy Cholesterol (27 HC) was added. The compound was also found to cause similar effects in mice in which human cancer cells had been implanted or genetically engineered to carry genes responsible for breast tumour. The research by Mc Donnel's team also revealed the ability of 27 HC to increase the metastasis.
Shaul's team conducted studies in women who were affected. When breast tissue samples of affected women were checked, it was found to have more 27 HC than unaffected women of the control group. The team was also able to zero in the enzyme responsible for the conversion of cholesterol to 27 Hydroxy cholesterol to be CYP27A1. Inversely, when the enzyme responsible for the breakdown of 27 HC, i.e; CYP7B1 was low, the survival period of affected women were significantly lowered. In severe cases, the amount of CYP27A1 was higher.
Thus, researchers were able to establish the role of 27 HC in causing and spreading cancer especially even when estrogen levels were lower thus providing an alternative route and risk in estrogen dependent tumours.
Mc Donnel and his team conducted further experiments in mice for understanding the exact mechanism. Genetically altered mice with implanted breast cancer cells were fed with a high fat diet and were found to carry more blood cholesterol as well as more 27 HC. The tumours which developed in such mice were also 30 % larger after a period of 15 days when compared to control group. Statins for lowering blood cholesterol were found to be effective in blocking the development of tumours.
Statins are drugs which are used to control blood cholesterol levels in obese patients. These drugs along with dietary modifications can therefore reduce the risk or slower the development of tumour especially in those which are estrogen dependent like breast cancer. This also provides the reason for non effectiveness of aromatase inhibitors which inhibit production of estrogen in some breast cancer patients. Statins or similar inhibitors of CYP27A1 can therefore be an ideal replacement for such patients.
Further studies are needed to reveal the link between 27 HC and other hormone dependent or hormone-driven cancers. Shaul's team has found that endometrial cancer cells too proliferate faster when supplied with 27 HC in petridish.
About Author / Additional Info:
1. JOCELYN KAISER; Cholesterol Forges Link Between Obesity and Breast Cancer; 29 NOVEMBER 2013 VOL 342 SCIENCE www.sciencemag.org
2. Mc Donnel; 27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology; Science 29 November 2013: Vol. 342 no. 6162 pp. 1094-1098