Statin use has been associated with a reduced incidence of colorectal cancer and might also affect survival of patients diagnosed with colon cancer.
Statins are believed to inhibit Ras signaling and may also activate the bone morphogenetic protein (BMP) signaling pathway in colorectal cancer cells.
Dr James Hardwick and colleagues from the Netherlands investigated the effects of statins on overall survival of patients with a diagnosis of colon cancer, and whether their effects were associated with changes in KRAS or the BMP signaling pathways.
Data were derived from the PHARMO database network (Netherlands) and linked to patients diagnosed with colon cancer from 2002 through 2007, listed in the Eindhoven Cancer Registry.
The research team obtained information on causes of death from statistics Netherlands.
|21% were defined as statin users after diagnosis of colon cancer|
The team constructed a tissue microarray of 999 colon cancer specimens from patients who underwent surgical resection from 2002 through 2008.
Survival was analyzed with statin user status after diagnosis as a time-dependent covariate.
Tumor tissues were analyzed by immunohistochemistry for levels of SMAD4, BMPR1A, BMPR1B, and BMPR2 proteins.
Tumor tissues were considered to have intact BMP signaling if they contained SMAD4 plus BMPR1A, BMPR1B, or BMPR2.
DNA was isolated from tumor tissues and analyzed by quantitative polymerase chain reaction to detect mutations in KRAS.
The team's primary outcome measures were overall mortality and cancer-specific mortality.
In this cohort, 21% of the patients were defined as statin users after diagnosis of colon cancer.
Statin use after diagnosis was significantly associated with reduced risk of death from any cause, and death from cancer.
The researchers observed that statin use after diagnosis was associated with reduced risk of death from any cause or from cancer for patients whose tumors had intact BMP signaling, but not for patients whose tumors did not have BMP signaling.
Statin use after diagnosis was not associated with reduced risk of death from any cause or from cancer for patients whose tumors did not contain KRAS mutations or whose tumors did have KRAS mutations.
Dr Hardwick's team comments, "In an analysis of 999 patients with a diagnosis of colon cancer, we associated statin with reduced risk of death from any cause or from cancer."
"The benefit of statin use is greater for patients whose tumors have intact BMP signaling, independent of KRAS mutation status. Randomized controlled trials are required to confirm these results."