Details

Autor(en) / Beteiligte

• Voorneveld, Philip W., MD
• Reimers, Marlies S., MD PhD
• Bastiaannet, Esther, PhD
• Jacobs, Rutger J., MD, PhD
• van Eijk, Ronald, PhD
• Zanders, Marjolein M.J., MD
• Herings, Ron M.C., PhD
• van Herk-Sukel, Myrthe P.P., PhD
• Kodach, Liudmila L., MD, PhD
• van Wezel, Tom, PhD
• Kuppen, Peter J.K., PhD
• Morreau, Hans, MD, PhD
• van de Velde, Cornelis J.H., MD, PhD
• Hardwick, James C.H., MD, PhD
• Liefers, Gerrit Jan, MD, PhD

Titel

Statin Use After Diagnosis of Colon Cancer and Patient Survival

Ist Teil von

• Gastroenterology (New York, N.Y. 1943), 2017-08, Vol.153 (2), p.470-479.e4

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2017

Quelle

ScienceDirect

Beschreibungen/Notizen

• Abstract Background & Aims 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 also activate the bone morphogenetic protein (BMP) signaling pathway in colorectal cancer cells. We 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. Methods 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. We obtained information on causes of death from statistics Netherlands. We 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. Multivariable Poisson regression survival models and Cox analyses were used to study the effect of statins on survival. 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 PCR to detect mutations in KRAS. The primary outcome measures were overall mortality and cancer-specific mortality. Results In this cohort, 21.0% of the patients (210/999) were defined as statin users after colon cancer diagnosis. Statin use after diagnosis was significantly associated with reduced risk of death from any cause (adjusted relative risk [RR], 0.67; 95% CI, 0.51–0.87; P=.003) and death from cancer (adjusted RR, 0.66; 95% CI, 0.49-0.89; P=.007). 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 (adjusted RR, 0.39; 95% CI, 0.22–0.68; P=.001), but not for patients whose tumors did not have BMP signaling (adjusted RR, 0.81; 95% CI, 0.55–1.21; P=0.106; P<.0001 for the interaction). 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 (adjusted RR, 0.81; 95% CI, 0.56–1.18; P=.273) or whose tumors did have KRAS mutations (adjusted RR, 0.59; 95% CI 0.35–1.03; P=.062; P for the interaction=0.90). Conclusions 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.