High-grade Prostate Cancer Risk Again Linked to Cholesterol

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Each 10 mg/dL increase in serum levels of total and HDL cholesterol are associated with a significant 5% and 14% increased risk of high-grade PCa, respectively.
Each 10 mg/dL increase in serum levels of total and HDL cholesterol are associated with a significant 5% and 14% increased risk of high-grade PCa, respectively.

High serum levels of total and HDL cholesterol are associated with an elevated risk of high-grade prostate cancer (PCa), researchers concluded.

In a post-hoc analysis of data from 4974 non-statin-using men in the REDUCE (Reduction by Dutasteride of prostate Cancer Events) trial, a team led by Stephen J. Freedland, MD, of Cedars-Sinai Medical Center in Los Angeles, found that each 10 mg/dL increase in serum total and HDL cholesterol is associated with a significant 5% and 14% increased odds of a diagnosis of high-grade PCa, respectively. The investigators found no association between total serum cholesterol and overall or low-grade PCa and between LDL cholesterol and the risk of any PCa.

The new study provides “yet one more reason for people to watch their cholesterol and dovetails with some data that statins may have benefits for prostate cancer,” Dr Freedland told Renal & Urology News.

Unlike previous research that found the same association, the new study focused on patients who underwent trial-mandated prostate biopsies independent of PSA, thus eliminating a potential source of bias, according to Dr Freedland's team. The REDUCE study was a randomized trial that enrolled men with elevated PSA and a negative baseline prostate biopsy. Men underwent 2- and 4-year trial-mandated prostate biopsies.

Each 10 mg/dL increment in total serum cholesterol was associated with a significant 5% increased odds of a diagnosis of high-grade PCa, Dr Freedland and his colleagues reported online in Prostate Cancer and Prostatic Diseases. The authors commented that, given the anti-inflammatory, anti-proliferative, and antioxidant properties of HDL, it is unclear why high HDL would be associated with an increased risk of PCa.

“Our findings demonstrate an association between high serum cholesterol and HDL and increased risk of high-grade prostate cancer in a setting where trial-mandated biopsies ensured complete cancer ascertainment,” Dr Freedland and his colleagues wrote. “These data support a role for cholesterol, a modifiable risk factor, in aggressive prostate cancer.”

Dr. Freedland's team explained that PCa is unique in its dependence on androgens for growth. “Cholesterol is the precursor for androgen synthesis by the prostate, leading to the hypothesis that increased serum cholesterol levels may be associated with a higher prostate cancer risk.”

Previous studies supporting a link between cholesterol and high-risk PCa include an analysis of the placebo arm of the Prostate Cancer Prevention Trial (PCPT), which demonstrated a reduced risk of high-grade PCa among men with lower cholesterol levels. Further, in a study of 55,875 patients at the Veterans Affairs New England Healthcare System, researchers found that, compared with men taking antihypertensive medications, men taking statins had a 31%, 14%, and 60% decreased risk of being diagnosed with any PCa, low-risk PCa, and high-risk PCa, respectively, according to a report in the Journal of the National Cancer Institute (2011;103;885-892).

Each 10 mg/dL increase in baseline total cholesterol was associated with a 2% increased risk of any PCa and 6% increased risk of high-grade PCa. In addition, the highest quartile of total cholesterol at baseline was associated with a 45% increased risk of total PCa and 3-fold increased risk of high-grade PCa. The highest quartile of HDL at baseline was associated with a 45% increased risk of total PCa and nearly 2.6-fold increased risk of high-grade PCa.

Reference

Jamnagerwalla J, Howard LE, Allott EH, et al. Serum cholesterol and risk of high-grade prostate cancer: results from the REDUCE study. Prostate Cancer Prostatic Dis. 2017; published online ahead of print.

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