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Table 3 Colorectal cancer patient mortality according to KRAS mutation status in 1067 BRAF -wild-type cases

From: Analyses of clinicopathological, molecular, and prognostic associations of KRAS codon 61 and codon 146 mutations in colorectal cancer: cohort study and literature review

KRAS Total No. Colorectal cancer-specific mortality Overall mortality
No. of events Univariate HR (95% CI) Multivariate stage-stratified HR (95% CI) No. of events Univariate HR (95% CI) Multivariate stage-stratified HR (95% CI)
Wild-type (codons 12, 13, 61 and 146) 582 144 1 (referent) 1 (referent) 258 1 (referent) 1 (referent)
All mutants together 485 163 1.46 (1.17-1.83) 1.19 (0.94-1.51) 256 1.32 (1.11-1.57) 1.14 (0.95-1.38)
    P = 0.0009    P = 0.0018  
Codons 12 and 13, and codons 61 and 146        
Codons 12 and 13 434 151 1.51 (1.20-1.90) 1.27 (0.99-1.62) 235 1.36 (1.14-1.62) 1.15 (0.95-1.40)
    P = 0.0004    P = 0.0007  
Codons 61 and 146 51 12 1.02 (0.57-1.85) 0.85 (0.47-1.56) 21 1.00 (0.64-1.56) 1.07 (0.68-1.68)
Codons 12, 13, 61 and 146        
Codon 12 mutants 328 121 1.64 (1.29-2.09) 1.45 (1.12-1.87) 183 1.45 (1.20-1.76) 1.24 (1.01-1.52)
    P < 0.0001 P = 0.0048   P = 0.0001 P = 0.037
Codon 13 mutants 106 30 1.16 (0.78-1.72) 0.83 (0.55-1.25) 52 1.11 (0.82-1.49) 0.90 (0.66-1.24)
Codon 61 mutants 16 4 1.11 (0.41-3.01) 0.81 (0.29-2.26) 8 1.43 (0.71-2.90) 1.55 (0.75-3.18)
Codon 146 mutants 35 8 0.98 (0.48-2.01) 0.86 (0.42-1.78) 13 0.84 (0.48-1.48) 0.88 (0.50-1.56)
The 10 most common mutations in codons 12, 13, 61 and 146     
c.34G>A (p.G12S) 12 6 2.44 (1.07-5.54) 0.94 (0.39-2.23) 7 1.57 (0.74-3.33) 0.77 (0.35-1.70)
    P = 0.033     
c.34G>C (p.G12R) 7 5 5.25 (2.13-12.9) 3.44 (1.25-9.43) 6 4.69 (2.06-10.6) 3.51 (1.42-8.70)
    P = 0.0003 P = 0.017   P = 0.0002 P = 0.0067
c.34G>T (p.G12C) 42 16 1.70 (1.01-2.86) 2.33 (1.36-3.99) 25 1.56 (1.03-2.35) 1.57 (1.02-2.42)
    P = 0.044 P = 0.0021   P = 0.035 P = 0.039
c.35G>A (p.G12D) 155 51 1.46 (1.06-2.01) 1.18 (0.84-1.66) 80 1.37 (1.06-1.76) 1.16 (0.89-1.51)
    P = 0.021    P = 0.015  
c.35G>C (p.G12A) 19 6 1.28 (0.56-2.90) 0.61 (0.26-1.42) 9 1.00 (0.51-1.95) 0.59 (0.30-1.17)
c.35G>T (p.G12V) 92 37 1.76 (1.22-2.52) 2.13 (1.47-3.09) 56 1.54 (1.16-2.06) 1.54 (1.14-2.08)
    P = 0.0024 P < 0.0001   P = 0.0033 P = 0.0048
c.38G>A (p.G13D) 101 30 1.23 (0.83-1.82) 0.83 (0.55-1.26) 50 1.14 (0.84-1.54) 0.91 (0.66-1.25)
c.183A>C (p.Q61H) 7 2 1.06 (0.26-4.28) 0.46 (0.11-1.93) 4 1.28 (0.48-3.45) 1.16 (0.42-3.18)
c.436G>A (p.A146T) 21 3 0.55 (0.17-1.71) 0.50 (0.16-1.59) 5 0.45 (0.19-1.10) 0.51 (0.21-1.26)
c.437C>T (p.A146V) 11 4 1.94 (0.72-5.26) 1.77 (0.64-4.90) 7 2.02 (0.95-4.29) 2.10 (0.97-4.56)
  1. The multivariate, stage-stratified Cox regression model initially included sex, age, body mass index, year of diagnosis, family history of colorectal cancer, tumor location, tumor differentiation, peritumoral lymphocytic reaction, microsatellite instability, CpG island methylator phenotype, PIK3CA mutation, and LINE-1 methylation. A backward elimination with a threshold of P = 0.20 was used to select variables in the final model.
  2. For the survival analysis of mutations in the two groups of KRAS codons (codons 12 and 13, and codons 61 and 146), the P-value for significance was adjusted for multiple hypothesis testing to P = 0.05/2 = 0.025. Thus, a P-value between 0.05 and 0.025 should be regarded as of borderline significance. For the survival analysis of mutations in the four KRAS codons (12, 13, 61 and 146), the P-value for significance was adjusted for multiple hypothesis testing to P = 0.05/4 = 0.013. Thus, a P-value between 0.05 and 0.013 should be regarded as of borderline significance. For the survival analysis of the 10 most common KRAS mutations, the P-value for significance was adjusted for multiple hypothesis testing to P = 0.05/10 = 0.005. Thus, a P-value between 0.05 and 0.005 should be regarded as of borderline significance. CI, confidence interval; HR, hazard ratio.