Exploring Cholesterol, Fat Tissue and Prostate Cancer

Prostate cancer incidence varies depending upon location and race, with US black men facing higher incidence and mortality than nonblacks. Obesity is linked to higher risk of aggressive prostate cancer, but cholesterol levels may play a role in these race disparities, says Emma H. Allott, PhD, a molecular epidemiologist who is a Marilyn Gentry Fellow in Nutrition and Cancer at the University of North Carolina at Chapel Hill. Here, Allott, shares what her research is uncovering about race, adipose tissue and tumor growth.

Q: How did you become interested in obesity and cancer risk?

A: I was interested in science early on and I've always been interested in obesity and nutrition. There was a PhD program in Dublin [Ireland]; it was a new program where you could visit different labs and choose your project. That's where I had the idea to focus on obesity and cancer.

Q: A lot of your current work is on cholesterol and prostate cancer. Can you briefly explain the link?

A: It’s an interesting relationship: prostate cancer, at least in the early stage, is a hormone dependent cancer and cholesterol is the precursor for hormone synthesis. The body uses cholesterol to generate sex hormones like testosterone, which is what causes early prostate cancer to progress.

The treatment [for this cancer] reduces hormones in the body. But the prostate can still use cholesterol to make its own hormones even while the person is taking drugs to lower the levels. This might be one mechanism for how the tumor can progress.

"African Americans are more likely to have heart disease for which high cholesterol is a risk factor. So since we think cholesterol may also play a role in prostate tumor progression, this may be one of the mechanisms."

Q: How could this relate to racial disparities in prostate cancer?

A: We know African American men have more aggressive prostate cancers and higher rates of mortality. Access to care is one factor, but maybe there’s something different in their biology. African Americans are more likely to have heart disease for which high cholesterol is a risk factor. So since we think cholesterol may also play a role in prostate tumor progression, this may be one of the mechanisms.

We have seen that PSA levels are correlated with serum cholesterol and there is a difference among black and white men. For prostate cancer recurrence, we’ve seen racial differences related to cholesterol levels.

Q: And that’s why you’re looking at how cholesterol-lowering drugs, like statins, affect risk?

A: Yes, epidemiologic data suggest that statin use is associated with lower prostate cancer risk. If cholesterol were involved in prostate cancer, you would expect that statin use lowers risk. Indeed, it looks like it does.

I’ve just done a study that looks at statin use and racial differences in prostate cancer aggressiveness at diagnosis. The population was about a 50-50 mix, with white and African American men. Statin use was associated with reduced prostate cancer aggressiveness in both races, with the strongest inverse associations in non-smokers.

Q: Are you looking at diet and other factors that can affect cholesterol?

A: Of course there is a large genetic component to high cholesterol and a few lifestyle determinants as well. High calorie intake is associated with high cholesterol as is having a high-intake of saturated fat.

We are looking at this but it's challenging in some of these observational studies. We have serum cholesterol levels, but we don’t have dietary information or genetics and we can’t adjust for these things; they could explain our associations but we can’t tell. In the meantime, we're looking at saturated fat intake.

Q: What are you finding?

A: We see that higher saturated fat is associated with more aggressive prostate cancer at diagnosis. This is regardless of race.

Q: You also research obesity and breast cancer. What does the latest research show here?

A: It’s not a straightforward association between obesity and breast cancer: it protects in premenopausal and increases risk in postmenopausal. Breast cancer seems to be two diseases: one type is ER positive and the other is ER negative. When you look at the association between obesity, we see it with ER positive, which often occurs later in life.

I think tumor subtyping is how we need to think of this going forward and that is definitely something I’d like to research further.

Q: Aside from statins, what can men do to lower their cholesterol levels and prostate cancer risk?

A: The lifestyle changes to adopt that may reduce risk of prostate cancer also offer benefits for other types of cancers and diseases, such as cardiovascular disease. Exercising,maintaining a healthy weight, and eating less saturated fat are all good for overall health.

Study references:

Allott EH, Hursting SD. Obesity and cancer: mechanistic insights from transdisciplinary studies. Endocr Relat Cancer. 2015 Dec;22(6):R365-86. doi: 10.1530/ERC-15-0400. Epub 2015 Sep 15. Review.

E H Allott, L Arab, L J Su, L Farnan, E T H Fontham, J L Mohler, J T Bensen and S E Steck. Saturated fat intake and prostate cancer aggressiveness: results from the population-based North Carolina-Louisiana Prostate Cancer Project. Prostate Cancer and Prostatic Diseases , (6 September 2016).

Allott EH, Farnan L, Steck SE, Arab L, Su LJ, Mishel M, Fontham ET, Mohler JL, Bensen JT. Statin Use and Prostate Cancer Aggressiveness: Results from the Population-Based North Carolina-Louisiana Prostate Cancer Project. Cancer Epidemiol Biomarkers Prev. 2016 Apr;25(4):670-7. doi: 10.1158/1055-9965.EPI-15-0631. Epub 2016 Jan 27.

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    Published on September 7, 2016

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