KRAS-mutation status in relation to colorectal cancer survival: the joint impact of correlated tumour markers

• Published in: British journal of cancer Vol. 108; no. 8; pp. 1757 - 1764
• Main Authors: PHIPPS, A. I, BUCHANAN, D. D, MAKAR, K. W, WIN, A. K, BARON, J. A, LINDOR, N. M, POTTER, J. D, NEWCOMB, P. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 30.04.2013
• Subjects: Adult; Aged; Biological and medical sciences; Biomarkers; Cancer research; Cancer therapies; Colorectal cancer; Colorectal Neoplasms - epidemiology; Colorectal Neoplasms - genetics; Colorectal Neoplasms - mortality; Epidemiology; Female; Gastroenterology. Liver. Pancreas. Abdomen; Genes, ras; Genetics and Genomics; Humans; Male; Medical prognosis; Medical research; Medical sciences; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Mutation; Population-based studies; SEER Program; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Survival Rate; Tumors; Washington - epidemiology; Womens health; Young Adult; Washington; Queensland Australia; Australia; United States > US; microsatellite instability; Rectal disease; Colorectal cancer; Tumoral marker; Epidemiology; Osteoarticular system; K ras Gene; BRAF Gene; Cancerology; Microsatellite DNA; Intestinal disease; Genetics; Protooncogene; Mortality; BRAF; Malignant tumor; Joint; Survival; Colonic disease; C-Onc gene; Digestive diseases; Instability; KRAS; Mutation; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2013.118

Mutations in the Kirsten Ras (KRAS) oncogene are common in colorectal cancer (CRC). The role of KRAS-mutation status as a prognostic factor, however, is unclear. We evaluated the relationship between KRAS-mutation status and CRC survival, considering heterogeneity in this association by tumour and patient characteristics. The population-based study included individuals diagnosed with CRC between 1998-2007 in Western Washington State. Tumour specimens were tested for KRAS exon 2 mutations, the BRAF p.V600E mutation, and microsatellite instability (MSI). We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between KRAS-mutation status and disease-specific and overall survival. Stratified analyses were conducted by age, sex, tumour site, stage, and MSI. We conducted additional analyses combining KRAS-mutation, BRAF-mutation, and MSI status. Among 1989 cases, 31% had KRAS-mutated CRC. Kirsten Ras (KRAS)-mutated CRC was associated with poorer disease-specific survival (HR=1.37, 95% CI: 1.13-1.66). This association was not evident in cases who presented with distant-stage CRC. Cases with KRAS-wild-type/BRAF-wild-type/MSI-high CRC had the most favourable prognosis; those with CRC exhibiting a KRAS- or BRAF-mutation and no MSI had the poorest prognosis. Patterns were similar for overall survival. Kirsten Ras (KRAS)-mutated CRC was associated with statistically significantly poorer survival after diagnosis than KRAS-wild-type CRC.