HDL Cholesterol and Cancer

June 15, 2010 (Boston, Massachusetts) — An inverse and significant association exists between levels of high-density lipoprotein (HDL) cholesterol and the risk of incident cancer, according to the results of a new analysis [1]. Researchers report that even after adjustment for multiple variables, there was a 36% lower risk of cancer for every 10-mg/dL increase in HDL cholesterol.

The researchers, including Drs Richard Karas and Alawi Alsheikh-Ali (Tufts University School of Medicine, Boston, MA), previously reported an inverse and significant association between on-treatment LDL [low-density lipoprotein]-cholesterol levels and cancer in statin-treated patients. That study, reported by heartwire , also showed a similar relationship between LDL-cholesterol levels and incident cancer among control patients not treated with statins, suggesting that statin therapy, despite significantly reducing LDL-cholesterol levels, was not associated with an increased risk of cancer.

"One of the limitations of the previous study with low LDL cholesterol and cancer risk was that people with low levels of LDL cholesterol are unlikely to die of heart disease," Karas told heartwire . "They're not dying of heart disease, so they're just around and therefore available to get cancer. With the HDL story, that's not the case. People with high levels of HDL cholesterol are unlikely to die of heart disease, but we found that they were also less likely to get cancer. It further strengthens the finding that there are these associations between cholesterol levels and cancer."

The new study, with first author Dr Haseeb Jafri (Tufts University School of Medicine), is published online June 14, 2010 in the Journal of the American College of Cardiology. To heartwire , Karas said that while his group had been thinking about the risk of cancer and LDL-cholesterol levels for a couple of years, there has been little research activity examining any links between HDL cholesterol and cancer.

Bigger Question About Cholesterol Levels and Cancer Risk

In this latest analysis, the researchers performed a meta-analysis of all lipid-intervention randomized, controlled trials with more than 1000 person-years of follow-up and baseline HDL-cholesterol levels and rates of incident cancer. They identified 24 clinical trials, among them the 4S, WOSCOPS, CARE, GISSI, ALLHAT-LLT, CORONA, and JUPITER studies, with more than 625 000 person-years of follow-up and 8185 cases of incident cancer.

In the univariate random-effects meta-regression analysis, there was a significant inverse relationship between baseline HDL-cholesterol levels and the rate of incident cancer. For every 10-mg/dL increase in HDL cholesterol levels, there was a 28% reduction in the risk of cancer. In a model that controlled for other variables, including LDL cholesterol, age, body-mass index (BMI), sex, and smoking status, there was a significant 36% lower risk of cancer for every 10-mg/dL increase in HDL cholesterol.

"I want to underscore that these are associations, so we can never infer or assume that it's cause and effect," said Karas. "But with that important caveat, there are some very interesting ideas that provide biological plausibility for this. We know that oxidants promote cancer, and there are a lot of data that diets rich in antioxidants reduce the risk of cancer. HDL cholesterol has antioxidant properties, so it's possible that the antioxidant effects of higher levels of HDL cholesterol help to reduce the cancer risk."

In addition to protecting individuals via HDL's antioxidant properties, Karas told heartwire that "immune surveillance," the process in which white blood cells are on the lookout for abnormal cells, might also play a role. HDL cholesterol has positive effects on the immune system, and higher levels of HDL might be linked with improved immune surveillance, which could lower the risk of cancer.

Low HDL as a Marker of Chronic Disease

In an editorial accompanying the study [2], Dr Jennifer Robinson (University of Iowa, Iowa City) writes that in addition to the biological plausibility supporting the link between HDL cholesterol and the risk of cancer, reverse causality does not explain away the relationship between low HDL cholesterol and cancer. In addition, there is a dose response observed between the lower rates of cancer with increases in HDL cholesterol, providing support again for the association. Still, alternative explanations have not been ruled out yet, and no randomized trials--the gold standard for demonstrating causality--have been conducted thus far.

"Data from ongoing trials are needed before drawing any firm conclusions regarding the role of niacin or any other HDL-cholesterol–increasing drugs in either cardiovascular disease or cancer prevention," writes Robinson. "At this time, the evidence best supports low HDL cholesterol as a marker for an overall increased risk of chronic disease."

Karas added that the findings underscore the importance of reporting cancer rates in future lipid intervention trials.