Table 3. Overall Prevalence of NRAS Mutations in mCRC and Subgroups.
| N Studiese | Summary prevalence (95% CI) | P-Het; I2 | P value for heterogeneity within subgroups | |
|---|---|---|---|---|
| Overall | 49 | 4.1% (3.5% - 4.8%) | < 0.001; 56.0% | |
| Exon 2a | 6 | 2.3% (1.4% - 3.7%) | 0.127; 41.8% | |
| Codon 12b | 7 | 2.2% (1.6% - 3.0%) | 0.209; 28.7% | < 0.001f |
| Codon 13b | 4 | 0.7% (0.5% - 1.0%) | 0.927; 0.0% | |
| Exon 3a | 5 | 2.4% (1.1% - 5.0%) | 0.003; 75.5% | |
| Codon 61b | 10 | 3.6% (2.6% - 5.0%) | 0.065; 44.1% | |
| Exon 4a | 3 | 0.6% (0.1% - 3.9%) | 0.991; 0.0% | |
| P value between exonsc | 0.368 | |||
| Sex | ||||
| Male | * | * | * | * |
| Female | * | * | * | |
| Median age of study population | ||||
| < 62 | 12 | 3.7% (3.0% - 4.7%) | 0.863; 0.0% | 0.479 |
| ≥ 62 | 12 | 4.3% (3.2% - 5.6%) | 0.036; 47.1% | |
| Meta-regression on median age | 24 | 0.006 (-0.048 - 0.060) | N/A | 0.822 |
| Race | ||||
| < 88% White/Caucasian | * | * | * | * |
| ≥ 88% White/Caucasian | 3 | 5.8% (3.4% - 9.8%) | 0.954; 0.0% | |
| Study location | ||||
| Asia | 13 | 3.0% (2.0% - 4.5%) | 0.009; 54.5% | 0.108 |
| Australia | * | * | * | |
| Europe | 22 | 4.6% (3.7% - 5.8%) | < 0.001; 64.6% | |
| Multi-country | 3 | 5.8% (3.4% - 9.8%) | 0.954; 0.0% | |
| North America | 10 | 3.6% (2.9% - 4.5%) | 0.980; 0.0% | |
| Study design | ||||
| Observational | 39 | 3.9% (3.3% - 4.7%) | < 0.001; 61.9% | 0.105 |
| Clinical trial | 10 | 5.3% (3.9% - 7.1%) | 0.544; 0.0% | |
| Treatment status | ||||
| Partial population treated | 5 | 3.5% (2.1% - 6.0%) | 0.940; 0.0% | 0.840 |
| Complete population treated | 15 | 4.2% (3.3% - 5.3%) | 0.336; 10.5% | |
| Unknown/not treated | 29 | 4.1% (3.3% - 5.0%) | < 0.001; 69.5% | |
| Source | ||||
| Primary tumor | 8 | 3.4% (2.4% - 4.8%) | 0.026; 55.9% | 0.318 |
| Metastasis | 6 | 4.9% (3.4% - 7.0%) | 0.936; 0.0% | |
| Both primary tumors and metastases | 9 | 3.5% (2.5% - 4.9%) | 0.019; 56.3% | |
| Mutation assessment methodd | ||||
| High-resolution melting | 6 | 3.0% (1.7% - 5.1%) | < 0.001; 84.6% | |
| Mass spectrometry | 11 | 4.0% (3.2% - 5.0%) | 0.023; 51.8% | |
| Multiplex mutation assays | 4 | 4.2% (3.3% - 5.4%) | 0.233; 29.8% | |
| Mutant allele specific PCR | 7 | 4.3% (3.4% - 5.3%) | 0.253; 23.1% | |
| Next-generation sequencing | 8 | 4.9% (3.9% - 6.2%) | 0.309; 15.4% | |
| Other | 3 | 4.5% (2.6% - 7.6%) | 0.064; 63.6% | |
| Pyrosequencing | 9 | 5.1% (3.6% - 7.3%) | < 0.001; 72.4% | |
| Sanger/direct sequencing (PCR) | 20 | 4.5% (4.0% - 5.0%) | 0.483; 0.0% | |
| Strip assay | * | * | * | |
| Study quality score | ||||
| ≤ 16 | 29 | 3.8% (3.0% - 4.8%) | < 0.001; 69.0% | 0.151 |
| > 16 | 20 | 4.7% (4.0% - 5.5%) | 0.535; 0.0% | |
| Study time period | ||||
| Pre-2007 | * | * | * | |
| Includes 2007 | 9 | 3.7% (2.9% - 4.7%) | 0.447; 0.0% | 0.247 |
| Post-2007 | 26 | 4.5% (3.6% - 5.6%) | < 0.001; 63.2% | |
| Median length of follow-up time | ||||
| < 25 months | * | * | * | * |
| ≥ 25 months | 7 | 4.1% (3.0% - 5.5%) | 0.998; 0.0% | |
| Meta-regression on follow-up time | 0.000 (-0.012 - 0.012) | N/A | 0.957 |
aGlobal exon estimate (most global estimate for a given exon contained within a manuscript); bCodon specified in papers as existing within exon 1, exon 2, exon 3 or unspecified; cP values assess differences between global exon estimates only; dCategories not mutually exclusive as some studies used multiple forms of mutation assessment methods, P value not calculated; eIndividual 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; fP value assesses differences between codon estimates. *N < 3, insufficient studies to run a meta-analysis. mCRC: metastatic colorectal cancer; CI: confidence interval.