Hypercholesterolemia and Breast Cancer

It has been clearly established that obesity and the metabolic syndrome are risk factors for estrogen receptor (ER) positive breast cancer – a type of breast cancer in which the tumor cells bind the female hormone estrogen – in postmenopausal women.

This increased risk has been attributed to a number of factors including:

• Increased levels of insulin and insulin-like substances in the circulation
• Localized production of estrogen in adipose (fat) tissues
• The role of inflammatory substances like cytokines in enhancing tumor cell growth.

Recent studies have implicated hypercholesterolemia – high levels of cholesterol in the bloodstream – as a definitive risk factor in for estrogen receptor (ER) positive breast cancer in postmenopausal women.  Hypercholesterolemia correlates with obesity and together these conditions have been shown to increase morbidity.  In addition, it has been shown that disease-free survival is improved in those patients who were taking statins prior to diagnosis.  Statins are members of  a class of compounds designed to inhibit cholesterol production in the liver

Although it has been proposed that statins exert their effect by directly inhibiting tumor cell growth, the amount of circulating statins in individuals who use the drug at the typical dose level is far below the amount required to inhibit cancer cell growth as has been reported in–vitro  (in the laboratory).  Therefore, there must be some other explanation.  An understanding of the role of cholesterol in breast cancer pathology would be invaluable in regards to possible therapeutic approaches.  Dr. Eric R. Nelson and his colleagues from the Department of Pharmacology and Cancer Biology at the Duke Institute for Genome Sciences and Policy at Duke University in Durham, NC, have made a significant contribution in this regard.

Nelson and his group have shown that the actual substance that seems to be responsible for accelerating the growth of breast cancer tumors is a metabolite of cholesterol – 27-Hydoxycholesterol (27HC).  Furthermore, 27HC is a product of the action of the enzyme cytochrome P450 oxidase (CYP27A1).   The expressed level of CYP27A1 correlates well with tumor grade in breast cancer patients and inhibition of this enzyme had a positive impact on the suppression of tumor growth.

 

From this data, the authors conclude that lowering the level of circulating cholesterol or inhibiting its conversion to 27HC represent effective strategies in the treatment of estrogen receptor (ER) positive breast cancer in postmenopausal women.  This is, indeed, an important finding.

Carbon Dioxide Emissions from Areas of Tropical Deforestation

Although the levels in increased atmospheric carbon dioxide (CO²) as a direct outcome of the burning of fossil fuels have been extensively studied, the amount of CO² produced as a direct result of tropical deforestation has been inadequately examined.  In fact, emissions that are a direct result of anthropogenic land-use modifications represent the most ambiguous and under-studied of that set of human activities that impact the planetary carbon cycle.

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There are many factors that make this avenue of investigation particularly challenging.  They include the following:

• An assessment of the rates of deforestation in relation to the amount of carbon contained within soils and vegetation
• The methodology used in clearing carbon and the fate of the cleared material
• The response of the soil-based carbon pool to the deforestation
• The longer term impact of the drastic modification of land cover that results from tropical deforestation.

In order to more effectively quantitate the carbon emissions that are a direct result of tropical deforestation, Dr. Nancy L. Harris and her colleagues at the Ecosystem Services Unit of Winrock International in Arlington Virginia used satellite observations of the loss of forest cover and mapped forest carbon stocks.  With these tools and methodologies, this group was able to estimate gross carbon emissions in targeted tropical regions between the years 2000 and 2005.

The result they obtained from this systematic approach was 0.81 petagrams of carbon emissions per year – a petagram is equivalent to 1000 trillion grams.  This value corresponds to ~ 1.8 trillion pounds of carbon emissions per year.  The authors of this study believe that their approach serves as a much more reliable model for estimating global progress on curbing CO² emissions from deforestation.