Table 1. Overall Prevalence of KRAS Mutations in mCRC and Subgroups.
| N studiesf | Summary prevalence (95% CI) | P-Het; I2 | P value for heterogeneity within subgroups | |
|---|---|---|---|---|
| Overall | 288 | 35.9% (34.6% - 37.3%) | < 0.001; 92.6% | |
| Exon 1a | 14 | 35.5% (30.3% - 41.1%) | < 0.001; 75.4% | |
| Exon 2a | 76 | 39.1% (37.1% - 41.3%) | < 0.001; 85.4% | |
| Codon 12b | 24 | 29.1% (26.3% - 32.1%) | < 0.001; 86.2% | |
| Codon 12c | 50 | 29.0% (26.9% - 31.2%) | < 0.001; 83.9% | |
| Gly12Ala | 59 | 3.3% (2.7% - 3.9%) | < 0.001; 77.8% | < 0.001 |
| Gly12Arg | 36 | 0.9% (0.6% - 1.4%) | < 0.001; 82.9% | |
| Gly12Asp | 85 | 14.6% (13.3% - 16.1%) | < 0.001; 90.8% | |
| Gly12Cys | 61 | 3.5% (3.0% - 4.1%) | < 0.001; 76.1% | |
| Gly12Phe | 5 | 0.2% (0.1% - 0.6%) | 0.035; 61.3% | |
| Gly12Ser | 62 | 2.8% (2.2% - 3.6%) | < 0.001; 88.8% | |
| Gly12Val | 87 | 10.2% (9.1% - 11.4%) | < 0.001; 89.6% | |
| Other codon 12 | 15 | 0.9% (0.3% - 2.9%) | < 0.001; 96.9% | |
| Codon 13b | 19 | 9.0% (7.9% - 10.2%) | < 0.001; 62.7% | |
| Codon 13c | 39 | 8.6% (7.7% - 9.5%) | < 0.001; 55.2% | |
| Gly13Arg | 8 | 0.2% (0.1% - 0.7%) | 0.001; 72.0% | < 0.001 |
| Gly13Asp | 82 | 8.6% (7.6% - 9.6%) | < 0.001; 85.0% | |
| Gly13Cys | 15 | 0.7% (0.4% - 1.2%) | < 0.001; 82.7% | |
| Gly13Ser | 4 | 0.3% (0.0% - 4.8%) | < 0.001; 90.9% | |
| Gly13Val | 8 | 0.4% (0.1% - 1.8%) | < 0.001; 80.2% | |
| Exon 3a | 9 | 2.9% (1.9% - 4.4%) | 0.009; 60.9% | |
| Codon 61 | 14 | 2.7% (2.1% - 3.5%) | 0.001; 62.0% | |
| Gln61Arg | 4 | 0.4% (0.2% - 0.6%) | 0.810; 0.0% | 0.016 |
| Gln61His | 11 | 1.6% (0.7% - 3.5%) | < 0.001; 92.3% | |
| Gln61Leu | 5 | 0.7% (0.2 %- 2.2%) | 0.004; 73.9% | |
| Other codon 61 | 3 | 0.2% (0.0% - 1.8%) | < 0.001; 89.3% | |
| Exon 4a | 8 | 5.0% (4.1% - 6.2%) | 0.228; 25.2% | |
| Codon 146 | 9 | 2.5% (1.9% - 3.3%) | 0.134; 35.5% | |
| P value between exonsd | < 0.001 | |||
| Sex | ||||
| Male | 55 | 37.3% (35.1% - 39.7%) | < 0.001; 76.9% | 0.011 |
| Female | 57 | 42.2% (39.3% - 45.2%) | < 0.001; 81.7% | |
| Median age of study population | ||||
| < 62 | 77 | 37.0% (34.3% - 39.8%) | < 0.001; 92.6% | 0.544 |
| ≥ 62 | 102 | 36.0% (33.8% - 38.1%) | < 0.001; 90.6% | |
| Meta-regression on median age | 179 | 0.004 (-0.012 - 0.020) | N/A | 0.612 |
| Race | ||||
| < 88% White/Caucasian | 21 | 37.8% (32.4% - 43.4%) | < 0.001; 94.1% | 0.401 |
| ≥ 88% White/Caucasian | 17 | 34.1% (28.1% - 40.7%) | < 0.001; 91.1% | |
| Study location | ||||
| Asia | 64 | 31.8% (28.3% - 35.5%) | < 0.001; 93.2% | 0.025 |
| Australia | 7 | 27.3% (19.1% - 37.5%) | < 0.001; 97.9% | |
| Europe | 146 | 37.3% (35.2% - 39.3%) | < 0.001; 92.0% | |
| Multi-country | 21 | 39.4% (36.1% - 42.9%) | < 0.001; 88.2% | |
| North America | 47 | 36.4% (33.4% - 39.6%) | < 0.001; 88.9% | |
| South America | 3 | 37.2% (28.7% - 49.9%) | < 0.001; 70.8% | |
| Study design | ||||
| Observational | 226 | 35.0% (33.5% - 36.6%) | < 0.001; 92.9% | 0.004 |
| Clinical trial | 62 | 39.5% (36.9% - 42.1%) | < 0.001; 89.0% | |
| Treatment status | ||||
| Partial population treated | 10 | 27.5% (18.0% - 39.6%) | < 0.001; 95.0% | 0.115 |
| Complete population treated | 158 | 37.2% (35.6% - 38.9%) | < 0.001; 89.6% | |
| Unknown/not treated | 120 | 35.1% (32.9% - 37.4%) | < 0.001; 94.2% | |
| Source | ||||
| Primary tumor | 60 | 18.9% (15.6% - 22.7%) | < 0.001; 94.6% | 0.012 |
| Metastasis | 37 | 21.2% (16.4% - 27.0%) | < 0.001; 94.3% | |
| Both primary tumors and metastases | 42 | 26.5% (23.0% - 30.4%) | < 0.001; 96.4% | |
| Mutation assessment methode | ||||
| Gel electrophoresis methods | 13 | 41.1% (35.7% - 46.6%) | 0.001; 65.5% | |
| High-resolution melting | 18 | 28.8% (23.7% - 34.6%) | < 0.001; 97.3% | |
| Mass spectrometry | 17 | 36.0% (32.2% - 40.0%) | < 0.001; 92.2% | |
| Multiplex mutation assays | 20 | 36.4% (33.1% - 39.9%) | < 0.001; 87.2% | |
| Mutant allele specific PCR | 77 | 37.4% (35.1% - 39.8%) | < 0.001; 92.2% | |
| Next-generation sequencing | 11 | 29.7% (20.1% - 41.7%) | < 0.001; 97.1% | |
| Pyrosequencing | 38 | 37.2% (33.9% - 40.6%) | < 0.001; 88.9% | |
| Sanger/direct sequencing (PCR) | 144 | 35.5% (34.0% - 37.0%) | < 0.001; 86.3% | |
| Strip assay | 7 | 42.1% (38.9% - 45.3%) | 0.045; 53.4% | |
| Other | 16 | 44.0% (37.4% - 50.7%) | < 0.001; 96.3% | |
| Not reported | 14 | 40.3% (33.1% - 47.9%) | < 0.001; 96.1% | |
| Study quality score | ||||
| ≤ 16 | 172 | 35.0% (33.1% - 37.0%) | < 0.001; 94.5% | 0.073 |
| > 16 | 116 | 37.5% (35.7% - 39.3%) | < 0.001; 85.4% | |
| Study time period | ||||
| Pre-2007 | 22 | 35.5% (32.3% - 38.9%) | < 0.001; 63.9% | 0.105 |
| Includes 2007 | 115 | 36.0% (33.7% - 38.4%) | < 0.001; 90.0% | |
| Post-2007 | 61 | 39.3% (36.7% - 42.0%) | < 0.001; 91.5% | |
| Median length of follow-up time | ||||
| < 25 months | 29 | 34.6% (31.1% - 38.3%) | < 0.001; 80.9% | 0.608 |
| ≥ 25 months | 34 | 33.0% (28.1% - 38.3%) | < 0.001; 91.7% | |
| Meta-regression on follow-up time | 63 | 0.002 (-0.004 - 0.008) | N/A | 0.583 |
aGlobal exon estimate (most global estimate for a given exon contained within a manuscript); bCodon specified in papers as existing within exon 2; cCodon specified in papers as existing within exon 1, exon 2, or unspecified; dP values assess differences between global exon estimates only; eCategories not mutually exclusive as some studies used multiple forms of mutation assessment methods, P value not calculated; fIndividual studies may contribute multiple prevalence estimates derived from independent study arms; so N refers to the number of independent prevalence estimates included in summary measure and may exceed the actual number of studies. mCRC: metastatic colorectal cancer; CI: confidence interval.