Is KRAS mutation associated with interval colorectal cancers?

Colorectal cancers diagnosed in the interval after a complete colonoscopy may occur due to rapid tumor growth. Interval colorectal cancers are associated with microsatellite instability (MSI). Our aim was to study the association of KRAS mutation with interval colorectal cancers and MSI. We searched our institution's cancer registry for interval colorectal cancers, defined as colorectal cancers that developed within 5 years of a complete colonoscopy. These were frequency matched to patients with non-interval colorectal cancers. Archived cancer specimens were evaluated for KRAS mutations in codons 12 and 13 using sequencing, and MSI by sequencing microsatellite loci. Multivariable logistic regression was used to analyze the association between KRAS mutation status, MSI status and interval colorectal cancers. There were 63 interval and 131 non-interval colorectal cancers. KRAS mutation was present in 12.9% of interval cancers compared to 28.9% of non-interval cancers (P = 0.03). In multivariable logistic regression model, KRAS was inversely associated with interval cancers (OR 0.36; 95% CI 0.15-0.90). In Cox proportional hazards model, adjusting for age, tumor grade, TNM Stage and MSI status, we found no association between KRAS mutation and 5-year survival compared to cancers without KRAS mutation (HR 0.84; 95% CI 0.4-1.46; P = 0.5). KRAS mutation is inversely associated with interval cancers and with MSI, suggesting that it is a marker of the chromosomal instability pathway associated with slow tumor growth, and distinct from MSI rapidly growing cancers. Molecular characterization of colorectal cancers is helpful in determining underlying pathway and may determine therapy.