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Statins reduced risk in patients with SMAD4-expressing colorectal tumors
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Digestive Disease Week 2011
CHICAGO — Statins significantly reduced the risk for colorectal cancer in all patients, but patients with high SMAD4 mutation expression saw their risk fall by more than one-third, according to results from a study of Dutch patients.
The findings suggest that physicians using statin therapy to treat patients with colorectal cancer will have to tailor treatment based on the tumor's molecular characteristics, said Rutger J. Jacobs, MD, PhD, a fellow in the department of gastroenterology and hepatology at Leiden University Medical Centre in Leiden, the Netherlands, who presented the results Sunday during Digestive Disease Week 2011.
Researchers observed a 14% overall risk reduction in the statin group (RR=0.86; 95% CI, 0.76-0.98). They then analyzed the cancers of 300 randomly selected patients from each group for SMAD4 expression. Risk reduction in this subgroup was 34% (RR=0.66; 95% CI, 0.53-0.82).
"If we look at all colorectal cancers, we see a risk reduction associated with statins of 14%, which is in line with results published previously," Jacobs said. "But, as we hypothesized, when SMAD4 is not present, statins would not be able to work. If we look at the SMAD4-positive cancers, we have a risk reduction of 34%. For SMAD4-negative cancers, there is no difference risk in cancer development between statin users and controls."
Using the National Pathology Registry, which contains data on all patients diagnosed with colorectal cancer in the Netherlands, and the PHARMO drug record linkage system, which contains all drug prescriptions of registered patients, Jacobs and colleagues set out to compare tumors from patients who developed disease during statin therapy and with patients who developed colorectal cancer while not receiving statin therapy. They hypothesized that, if statins are growth inhibitory only in SMAD4-expressing tumors, the risk reduction in patients with that mutation should be significantly higher.
From 2000 to 2008, 69,272 patients used statins and beta-blockers and 94,753 used beta-blockers alone. There were 386 patients diagnosed with colorectal cancer in the statin group compared with 609 patients in the beta-blockers group.
Statin use has a moderate overall chemopreventive effect in colorectal cancer. It has no chemopreventive effect in SMAD4 low-expressing cancer, but a very strong effect in SMAD4-positive cancer. This is independent of KRAS or BRAF mutation status, the researchers said. – by Jason Harris
For more information:
- Jacobs RJ. #573. Presented at: Digestive Disease Week 2011; May 7-10, 2011; Chicago.
Disclosure: Dr. Jacobs reports no relevant financial disclosures.
In those people who got statins and expressed SMAD4 in the nucleus, there was less occurrence of colorectal cancer. That's a basic study finding, but whether that will translate into population screening is not known. These results suggest statins work through this pathway, and Dr. Jacobs showed some historical papers demonstrating that link, but we still need to see some experiments proving that SMAD4 alters the BMP pathway. It's an intriguing proof of concept, but it still needs validation.
– John M. Carethers, MD
Professor and
Chair of Internal Medicine,
University of Michigan Health System
Disclosure: Dr. Carethers reports no relevant financial disclosures.
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