BACKGROUND AND AIMS: @entity14 ( @entity14 ) is a heterogeneous disease that can develop via several pathways. Different @entity14 subtypes, identified based on @entity5 markers, have been proposed to reflect these pathways. We evaluated the significance of these previously proposed classifications to survival. METHODS: @entity1 in the population-based Seattle @entity694 Family Registry were diagnosed with invasive @entity14 from 1998 through 2007 in western Washington State (N  = 2706), and followed for survival through 2012. Tumor samples were collected from 2050 @entity1 and classified into 5 subtypes based on combinations of @entity5 markers: type 1 ( @entity124 [ @entity124 ]-high, CpG island methylator phenotype [CIMP] -positive, positive for @entity817 mutation, negative for @entity984 mutation); type 2 ( @entity124 [ @entity124 ] or @entity124 -low, CIMP-positive, positive for @entity817 mutation, negative for @entity984 mutation); type 3 ( @entity124 or @entity124 low, non-CIMP, negative for @entity817 mutation, positive for @entity984 mutation); type 4 ( @entity124 or @entity124 -low, non-CIMP, negative for mutations in @entity817 and @entity984 ); and type 5 ( @entity124 -high, non-CIMP, negative for mutations in @entity817 and @entity984 ). Multiple imputation was used to impute @entity5 markers for those missing data on 1-3 markers. We used Cox regression to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of subtypes with disease-specific and overall mortality, adjusting for age, sex, body mass, diagnosis year, and smoking history. RESULTS: Compared with @entity1 with type 4 @entity5 (the most predominant), @entity1 with type 2 @entity5 had the highest disease-specific mortality (HR  = 2.20, 95% CI: 1.47-3.31); subjects with type 3 @entity5 also had higher disease-specific mortality (HR  = 1.32, 95% CI: 1.07-1.63). Subjects with type 5 @entity5 had the lowest disease-specific mortality (HR  = 0.30, 95% CI: 0.14-0.66). Associations with overall mortality were similar to those with disease-specific mortality. CONCLUSIONS: Based on a large, population-based study, @entity14 subtypes, defined by proposed etiologic pathways, are associated with marked differences in survival. These findings indicate the clinical importance of studies into the molecular heterogeneity of @entity14 .

Association between molecular subtypes of @entity14 and XXXX survival.

@entity1 :: ('9606', 'Species') :: ['participants', 'Participants'] @entity124 :: ('MESH:D053842', 'Disease') :: ['microsatellite stable', 'MSI', 'microsatellite instability', 'MSS'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'tumors'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity14 :: ('MESH:D015179', 'Disease') :: ['Colorectal cancer', 'CRC'] @entity817 :: ('673', 'Gene') :: ['BRAF'] @entity694 :: ('MESH:D003110', 'Disease') :: ['Colon Cancer']
@entity1 :: (9606,Species) :: ['patient']
