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Cholesterol levels rather than statins may be linked to colorectal cancer risk
New research suggests that cholesterol levels influence colorectal cancer risk, not statin use as identified in previous studies. According to investigators, “indication bias” may explain the associations previously found between statins and reduced risk for colorectal cancer.
“There appears to be an artificially protective effect of statins,” Ronac Mamtani, MD, MSCE, an assistant professor of hematology/oncology from the Perelman School of Medicine at the University of Pennsylvania and the Abramson Cancer Center, said in a press release. “Although the risk of colorectal cancer was lower in statin users versus non-users, when we compared those who continued statin therapy versus those who discontinued the therapy, such that each group shared the same indication for statin therapy, there was no difference in risk.”
To explore the associations between statin use and reduced CRC risk, Mamtani and colleagues performed a nested case-control study involving 22,163 CRC cases and 86,538 matched controls in the U.K. identified using The Health Improvement Network. They used conditional logistic regression models to estimate CRC risk with use of statins, serum total cholesterol and change in total cholesterol level.
First, they found that a reduced risk for CRC was associated with long-term statin use (OR = 0.95; 95% CI, 0.91-0.99) and short-term statin use (OR = 0.92; 95% CI, 0.85-0.99), confirming findings from previous studies.
However, a subgroup analysis of 5,102 CRC cases and 19,032 controls who were prescribed statins showed CRC risk did not differ significantly between those who discontinued statin therapy (3.1% of each group) vs. those who continued statin therapy (OR = 0.98; 95% CI, 0.79-1.22), suggesting that indication bias may explain the previous associations.
They also observed an independent association between increased serum cholesterol and reduced CRC risk (OR = 0.89 per mmol/L increase; 95% CI, 0.87-0.91), but only when serum cholesterol was measured close to the cancer diagnosis (less than 6 months, OR = 0.76; 95% CI, 0.47-0.61 vs. more than 24 months, OR = 0.98; 95% CI, 0.93-1.03).
Moreover, they found reductions in serum total cholesterol of more than 1 mmol/L at least a year before cancer diagnosis were associated with subsequent CRC in both statin users (OR = 1.25; 95% CI, 1.03-1.53) and nonusers (OR = 2.36; 95% CI, 1.78-3.12).
As this was an observational study, the researchers acknowledge its limitations include incomplete data and residual confounding.
“Together, these data demonstrate a complex association between statins, cholesterol, and colorectal cancer,” Mamtani said in the press release. “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.” – by Adam Leitenberger
Disclosure: Mamtani reports receiving personal fees from Takeda outside of this study. Please see the full study for a list of all other researchers’ relevant financial disclosures.