Table 1.

Studies on prognostic significance of KRAS codon 12 and 13 mutations in colorectal cancer

No. of KRAS mutantsMultivariate HR (95% CI; vs. KRAS-
Ref.Authors (y)No. of hospitalsSample sizeTumor locationDisease stagecodon 12 (No. of events)codon 13 (No. of events)BRAF datawild-type as a referent, unless otherwise specified)Notes
16Samowit and colleagues (2000)Many1,413ColonI–IV353 (–)100 (–)NoCancer-specific survivalAdjusted by age and stage.
Codon 12, 1.0 (0.8–1.2)
Codon 13, 1.4 (0.95–2.0)
c.35G>A, 1.1 (0.8–1.5)
c.35G>T, 0.8 (0.5–1.2)
c.38G>A, 1.4 (0.95–2.0)
17Andreyev and colleagues (2001; Meta-analysis)<352,832Colon and rectumI–IV<900 (<395)<297 (<139)NoOverall survivalAdjusted by age, stage, and center.
c.34G>A, 1.20 (0.86–1.70)
c.34G>T, 1.26 (0.93–1.62)
c.35G>A, 0.94 (0.79–1.11)
c.35G>C, 1.35 (0.98–1.87)
c.35G>T, 1.29 (1.08–1.55)
c.38G>A, 0.93 (0.78–1.12)
18Bazan and colleagues (2002)1160Colon and rectumI–IV40 (21)34 (28)NoCancer-specific survivalCovariates were location, stage, surgical resection, nodal metastasis, tumor growth pattern, lymphovascular invasion, lymphocytic infiltration, DNA aneuploidy status, and synthesis phase fraction status.
Codon 13, 1.93 (1.17–3.18)
19Roth and colleagues (2010)Many1,299ColonII–III372 (–)102 (–)NoRelapse-free survivalAdjusted by treatment arm and stage.
c.34G>A, 0.99 (0.46–2.09)
c.34G>T, 1.40 (0.89–2.21)
c.35G>A, 0.98 (0.72–1.34)
c.35G>C, 0.97 (0.48–1.95)
c.35G>T, 1.09 (0.76–1.57)
c.38G>A, 0.99 (0.68–1.44)
20Zlobec and colleagues (2010)2392Colon and rectumI–III71 (–)27 (–)NoCancer-specific survivalCovariates were tumor depth, nodal metastasis, and MSI.
c.35G>A, HR = 0.82 (P = 0.044)
21Yokota and colleagues (2011)1229Colon and rectumAdvanced and recurrence53 (–)26 (–)YesUnivariate HR for overall survival (vs. KRAS wild-type/BRAF wild-type as a referent; no multivariate HR provided)Multivariate analysis included both BRAF mutants and BRAF wild-type tumors. Covariates were age, sex, performance status, BRAF, pathologic type, number of metastasis, and presence of metastasis (liver, lung, and peritoneum).
Codon 12, 1.28 (0.74–2.19)
Codon 13, 2.03 (1.10–3.74)
Imamura and colleagues (current study)Many1,261 (1075 BRAF-wild-type tumors)Colon and rectumI–IV332 (119)108 (31)YesCancer-specific survival (vs. KRAS wild type/BRAF wild type as a referent)Adjusted by stage; covariates were age, sex, year of diagnosis, tumor location, tumor differentiation, family history of colorectal cancer in any first degree relative, MSI, CpG island methylator phenotype, PIK3CA, and LINE-1 methylation.
Codon 12, 1.29 (1.01–1.65)Codon 13, 0.86 (0.58–1.27)c.34G>A, 1.00 (0.42–2.34)c.34G>C, 3.21 (1.22–8.45)c.34G>T, 1.52 (0.90–2.58)c.35G>A, 1.09 (0.78–1.53)c.35G>C, 0.55 (0.24–1.28)c.35G>T, 1.94 (1.34–2.80)c.38G>A, 0.88 (0.59–1.30)