ORIGINAL ARTICLE Is BRAF Mutation Associated with Interval Colorectal Cancers? Aasma Shaukat • Mustafa Arain • Bharat Thaygarajan • John H. Bond • Mandeep Sawhney Received: 20 November 2009 / Accepted: 25 February 2010 / Published online: 19 March 2010 Ó Springer Science+Business Media, LLC 2010 Abstract Introduction Colon cancers diagnosed in the interval after a complete colonoscopy may occur due to limitations of colonoscopy or due to rapid tumor growth. The aim of this study was to compare the association of BRAF V600E mutation in interval versus non-interval colorectal cancers and to determine the relationship between BRAF mutation and 5-year survival. Methods We searched our institution’s cancer registry for interval cancers, defined as colon cancers that developed within 5 years of a complete colonoscopy. These were frequency matched to patients with non-interval cancers. Archived cancer specimens were tested for BRAF V600E mutation and MSI. Results There were 63 interval and 131 non-interval cancers. BRAF mutation was present in 28% of interval cancers compared to 19% of non-interval cancers (P = 0.18). In a multivariable logistic regression model, proximal location (OR 1.85; 95% CI 1.01–3.8) and MSI (OR 2.7; 95% 1.1–6.8) were independently associated with interval cancers while BRAF mutation was not (OR 0.93; 95% CI 0.36–2.38). BRAF mutation portended a poor 5-year survival, particularly among microsatellite stable cancers. Conclusions BRAF mutation is not associated with interval cancers but is a marker of poor prognosis, partic- ularly in microsatellite stable cancers. Keywords BRAF Á Colorectal cancer Á Interval cancer Introduction Colonoscopy is considered the gold standard test for the detection and prevention of colon cancer. Tumors that develop in the interval between serial colonoscopy (inter- val cancers) have a substantial negative impact on our ability to reduce the incidence of colon cancer. The development of interval cancers may represent extrinsic factors related to the procedure (reflecting limitations of colonoscopy) or intrinsic tumor characteristics resulting in rapid tumor growth. The Ras/Raf/MEK/ERK signaling pathway plays a vital role in the regulation of cell proliferation, differentiation, and survival. An activating mutation in the RAF gene, BRAF, leads to unregulated cell growth and tumor prolif- eration. Mutations of the BRAF gene have been reported in 9.5–23.5% of all sporadic colon cancers and are strongly associated with microsatellite instability (MSI) in sporadic colon cancers, but not in hereditary nonpolyposis colorectal cancer (HNPCC) [1, 2]. BRAF mutation is seen in microsatellite stable tumors as well and patients with this combination have been associated with a worse prognosis (poorer survival) than patients with the BRAF mutation in conjunction with MSI [1]. We have previously shown that A. Shaukat (&) Á M. Arain Á J. H. Bond Division of Gastroenterology, VA Medical Center, One-Veterans Drive, 111-D, Minneapolis, MN 55417, USA e-mail: shaukat@umn.edu A. Shaukat Á M. Arain Á J. H. Bond Department of Medicine, University of Minnesota, Minneapolis, MN, USA B. Thaygarajan Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, USA M. Sawhney Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA 123 Dig Dis Sci (2010) 55:2352–2356 DOI 10.1007/s10620-010-1182-9