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New Study Suggests Cholesterol Levels, Not Statins, Influence Colorectal Cancer Risk

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Key Points

  • Blood cholesterol levels were inversely related to colorectal cancer risk: the higher the cholesterol level, the lower the risk for patients, regardless of statin use.
  • An unexplained drop in cholesterol levels 1 year before a cancer diagnosis increased the risk of cancer in both statin users and nonusers.
  • Researchers also found that the difference in the risk of colorectal cancer was not significantly different between those patients who continued statin therapy and those who discontinued. Decreases in total serum cholesterol at least a year before the cancer diagnosis were associated with 1.25-fold and 2.36-fold increased risk of colorectal cancer in users and nonusers, respectively.

Long-term use of the cholesterol-lowering drugs statins does not appear to decrease a patient’s risk of colorectal cancer, suggests a new, large case-control study from Penn Medicine published by Mamtani et al in PLOS Medicine. The observational analysis of over 100,000 patients’ medical records suggests it is cholesterol levels that influence risk, not the much-debated statins, and that “indication bias” may explain the link between the widely-used cardiovascular drugs and risk.

“There appears to be an artificially protective effect of statins,” said Ronac Mamtani, MD, MSCE, Assistant Professor of Hematology/Oncology at the Abramson Cancer Center and the Perelman School of Medicine of the University of Pennsylvania, and lead author of the study. “Although the risk of colorectal cancer was lower in statin users vs nonusers, when we compared those who continued statin therapy vs those who discontinued the therapy, such that each group shared the same indication for statin therapy, there was no difference in risk.”

Statins are a common cholesterol-lowering treatment for patients at risk for coronary heart disease. Previous studies have also shown a potential reduction in cancer risk for people who take the drugs; however, they did not account for the blood cholesterol level on cancer risk, the authors said. Both statin use and high cholesterol have been linked to a lower colorectal cancer risk, but it has remained unclear which may be responsible for the apparent beneficial effects.

Study Findings

In the new study, the researchers compared statin use and blood cholesterol level between 22,163 patients with colorectal cancer and 86,538 patients without colorectal cancer from a database of electronic records of over 10 million patients from primary care practices in the United Kingdom.

Blood cholesterol levels were inversely related to colorectal cancer risk: the higher the cholesterol level, the lower the risk for patients, regardless of statin use, the authors found. The researchers also found that an unexplained drop in cholesterol levels 1 year before a cancer diagnosis increased the risk of cancer in both statin users and nonusers.

Researchers also found that the difference in the risk of colorectal cancer was not significantly different between those patients who continued statin therapy and those who discontinued (odds ratio = 0.98; 95% confidence interval = 0.79-1.22). Furthermore, for every 1 mmol/L (~38.6 mg/dl) increase in total cholesterol level, authors observed a 10% decreased risk of colorectal cancer.

Additionally, they observed that decreases in total serum cholesterol (>1 mmol/L) at least a year before the cancer diagnosis were associated with 1.25-fold and 2.36-fold increased risk of colorectal cancer in users and nonusers, respectively.

The findings point to a bigger role of cholesterol levels on cancer risk that could potentially serve as a blood biomarker to help diagnosis colorectal cancer earlier.

“Together, these data demonstrate a complex association between statins, cholesterol, and colorectal cancer,” Dr. Mamtani said. “While unexplained decreases in blood total cholesterol should alert physicians to consider colon cancer as one potential explanation, future studies are needed to determine the utility of blood cholesterol as a marker for early detection of colon cancer.”

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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