Two new studies from the US published this week negate concerns that have been around since early studies done decades ago suggested that low cholesterol leads to some types of cancer: one in fact affirms that undiagnosed cancer is the likely cause of lower total cholesterol while the other found evidence linking low cholesterol and decreased risk of high-grade prostate cancer among older men.

The two studies, along with an editorial discussing the new questions they raise, are published in the OnlineFirst 3 November issue of Cancer Epidemiology, Biomarkers & Prevention.

Dr Demetrius Albanes, a senior investigator at the National Cancer Institute in the US and co-author of the study that looked at the link between total and High-Density Lipoprotein cholesterol (HDL, sometimes called “good cholesterol”) and cancer risk said that while early studies suggested that low cholesterol might increase the risk of some cancers:

“Our study affirms that lower total cholesterol may be caused by undiagnosed cancer.”

He said the public health message from the study was that higher levels of “good” (HDL) cholesterol:

“Seem to be protective for all cancers, which is in line with recommendations for cardiovascular health.”

For the study, for 18 years, Albanes and colleagues followed 29,093 men taking part in the Alpha-Tocopheral, Beta-Carotene Cancer Prevention Study, the largest and longest of its kind.

During the follow up, they recorded 7,545 cases of cancer and found that:

  • Low total cholesterol was linked to an 18 per cent higher risk of cancer overall.

  • This figure is similar to the increases seen in previous studies.

  • But the risk disappeared when they excluded cases that occurred in the early years after the original blood samples were tested.

  • Higher levels of HDL cholesterol were linked to a 14 per cent decreased risk of cancer, even after excluding nine years of early cases.

The authors concluded that:

“Our findings suggest that prior observations regarding serum total cholesterol and cancer are largely explained by reverse causation.”

In other words, as Albanes explained to the press, it seems that it is not low total cholesterol causes cancer but that underlying cancer leads to low total cholesterol.

With respect to the HDL result, the authors cautiously concluded that:

“Although chance and reverse causation may explain some of the inverse HDL associations, we cannot rule out some etiologic role for this lipid fraction.”

So it appears that while they suggest higher HDL could be protecting people and lowering their risk of cancer, they can’t rule out that perhaps underlying cancer leads to lower levels of HDL as well as total cholesterol, and it is this effect that is showing in the figures.

In the other study, that focused on prostate cancer and cholesterol, researchers found a link between low cholesterol and decreased risk of high-grade prostate cancer among 5,586 men older than 55 years.

First author Dr Elizabeth Platz, said:

“High-grade prostate cancer is less common than prostate cancer overall, but it is a subset of prostate cancer that is more likely to progress.”

Platz is associate professor in the Department of Epidemiology at the Johns Hopkins Bloomberg School of Public Health and co-director of the Cancer Prevention and Control Program at the Sidney Kimmel Comprehensive Cancer Center at the Johns Hopkins University.

The results showed that:

  • Men with a total cholesterol level of less than 200 mg/dL had a 59 per cent lower risk of high-grade prostate cancer (Gleason score of 8 to 10).

  • There was no link between cholesterol levels and prostate cancer overall or for prostate cancer with a lower Gleason score.

Platz and colleagues concluded that:

“These prospective results support that men with low cholesterol have a reduced risk of high-grade prostate cancer.”

“These and other contemporary data that suggest that cholesterol metabolism should be investigated further in the etiology of prostate cancer,” they added.

Platz said their findings confirm the benefits of keeping cholesterol low among older men.

These studies are likely to impact the debate on statins, which have been heralded as one of the greatest success stories of the past few decades in that since their arrival on the public health scene, levels of cholesterol and rates of heart disease have gone down. These blockbuster drugs have also made their manufacturers a lot of money, who will inevitably push on the open door left for them by researchers, to find new applications for them.

Drs Eric J Jacobs and Susan M. Gapstur raise this point in an editorial accompanying the two studies. Jacobs, who is the the strategic director of pharmacoepidemiology at the American Cancer Society, said they had concluded that:

“Until there is evidence from randomized trials, men should not take statins in order to prevent high-grade prostate cancer.”

Jacobs said a randomized trial among men without prostate cancer would need to be very large and might not be feasible, but suggested that one possibility might be to conduct:

“A randomized trial among early stage prostate cancer patients opting for surveillance rather than immediate treatment, to see if statins could lower risk of prostate cancer progression.”

“Prediagnostic Total and High-Density Lipoprotein Cholesterol and Risk of Cancer.”
Jiyoung Ahn, Unhee Lim, Stephanie J. Weinstein, Arthur Schatzkin, Richard B. Hayes, Jarmo Virtamo, and Demetrius Albanes
Cancer Epidemiol Biomarkers Prev, 1055-9965.EPI-08-1248; Published OnlineFirst November 3, 2009
DOI:10.1158/1055-9965.EPI-08-1248

“Men with Low Serum Cholesterol Have a Lower Risk of High-Grade Prostate Cancer in the Placebo Arm of the Prostate Cancer Prevention Trial.”
Elizabeth A. Platz, Cathee Till, Phyllis J. Goodman, Howard L. Parnes, William D. Figg, Demetrius Albanes, Marian L. Neuhouser, Eric A. Klein, Ian M. Thompson, Jr, and Alan R. Kristal.
Cancer Epidemiol Biomarkers Prev, 1055-9965.EPI-09-0472; Published OnlineFirst November 3, 2009
DOI:10.1158/1055-9965.EPI-09-0472

“Cholesterol and Cancer: Answers and New Questions.”
Eric J. Jacobs and Susan M. Gapstur.
Cancer Epidemiol Biomarkers Prev, 1055-9965.EPI-09-1027; Published OnlineFirst November 3, 2009
DOI:10.1158/1055-9965.EPI-09-1027

Additional sources: American Association for Cancer Research.

Written by: Catharine Paddock, PhD