Table 2.
EGFR genotype and overall survival of NSCLC patients treated with TKIs.
| dbSNP-ID | Variant type, location, and/or consequence | Author, year (ref) | Genotyping platform used | Genotype | No. of patients (%) | Median OS (95% CI) in months | HR (95% CI) | RR (95% CI) |
|---|---|---|---|---|---|---|---|---|
| rs11534848 | Missense variant, 1562G>A, R521K | Zhang et al., 2013 [31] | MassARRAY system | AA | 48 (35.5) | 10.0 (4.2–15.8) | Reference | NA |
| AG | 66 (48.9) | 16.8 (7.0–26.6) | 1.53 (0.94–2.51) | NA | ||||
| GG | 21 (15.6) | 29.4 (4.9–53.9) | 1.84 (0.86–3.95) | NA | ||||
|
| ||||||||
| rs11568315 | Intron variant, g.55020560_55020561AC[n] | Giovannetti et al., 2010 [57] | TaqMan assay | Both alleles ≤ 16CA | 30 (31.9) | 7.9 (3.5–12.2) | NA | NA |
| At least 1 allele > 16CA | 64 (68.1) | 11.6 (6.5–16.7) | NA | NA | ||||
| Nie et al., 2011 [60] | PCR-RFLP and sequencing | At least 1 allele ≤ 16CA | 66 (57.4) | 15.9 (9.4–22.4) | NA | Reference | ||
| Both alleles > 16CA | 49 (42.6) | 10.7 (4.7–16.8) | NA | 0.81 (0.55–1.19) | ||||
| Tiseo et al., 2010 [58] | Fluorescent PCR and capillary electrophoresis | At least 1 allele = 16CA | 56 (74.0) | 12 (9.0–15.0) | Reference | NA | ||
| Both alleles ≠ 16CA | 20 (26.0) | 4 (1.0–8.0) | 1.95 (1.12–3.7) | NA | ||||
| Ichihara et al., 2007 [26] | PCR and sequencing | Short allele ≥ 19CA or the sum of alleles ≥ 39CA | 63 (64.3) | NA | Reference | NA | ||
| Short allele < 19CA or the sum of alleles < 39CA | 35 (35.7) | NA | 0.96 (0.50–1.86) | NA | ||||
| Kim et al., 2017 [61] | TaqMan assay and sequencing | Both alleles ≤ 16CA | 74 (28.0) | NA | Reference | NA | ||
| At least 1 allele > 16CA | 188 (72.0) | NA | 0.89 (0.64–1.24) | NA | ||||
| Liu et al., 2008 [56] | PCR-RFLP | At least 1 allele > 16CA | 59 (64.0) | NA | Reference | NA | ||
| Both alleles ≤ 16CA | 33 (36.0) | NA | 0.72 (0.45–1.16) | NA | ||||
| Winther Larsen et al., 2014 [59] | PCR-RFLP and capillary electrophoresis | Any allele ≤ 16CA | 44 (71.0) | 19.6 (11.9–27.3) | 0.43 (0.23–0.78) | NA | ||
| Both alleles > 16CA | 18 (29.0) | 8.4 (5.0–11.9) | Reference | NA | ||||
|
| ||||||||
| rs11977388 | Intron variant, g.150522T>C | Zhang et al., 2013 [31] | MassARRAY system | TT | 50 (39.4) | 13.2 (6.1–20.3) | Reference | NA |
| TC | 64 (50.4) | 16.8 (7.2–26.4) | 1.26 (0.80–2.00) | NA | ||||
| CC | 13 (10.2) | 16.5 (0.0–40.4) | 1.34 (0.56–3.18) | NA | ||||
|
| ||||||||
| rs2075102 | Intron variant, g.171581C>A | Zhang et al., 2013 [31] | MassARRAY system | CC | 90 (70.3) | 11.8 (5.9–17.7) | Reference | NA |
| CA | 33 (25.8) | 16.8 (12.8–20.8) | 0.91 (0.55–1.49) | NA | ||||
| AA | 5 (3.9) | 29.4 (NA) | 1.15 (0.34–3.90) | NA | ||||
|
| ||||||||
| rs2227983 | Missense variant, 1562G>A, R497K | Giovannetti et al., 2010 [57] | TaqMan assay | GG or GA | 81 (88.0) | 7.4 (6.5–8.4) | NA | NA |
| AA | 11 (12.0) | 8.0 (0.0–17.3) | NA | NA | ||||
| Nie et al., 2011 [60] | PCR-RFLP and sequencing | AA | 43 (37.4) | 17.4 (3.4–31.5) | NA | Reference | ||
| AG | 47 (40.9) | 14.3 (7.0–21.6) | NA | 0.81 (0.49–1.34) | ||||
| GG | 25 (21.7) | 12.3 (1.1–23.4) | NA | 0.71 (0.43–1.17) | ||||
| Liu et al., 2008 [56] | PCR-RFLP | AA | 43 (47.0) | NA | Reference | NA | ||
| GG or GA | 49 (53.0) | NA | 1.24 (0.74–1.95) | NA | ||||
| rs2293347 | Synonymous variant, 181946C>T, D994D | Zhang et al., 2013 [31] | MassARRAY system | GG | 59 (46.1) | 21.0 (14.0–27.9) | Reference | NA |
| GA | 59 (46.1) | 15.0 (8.3–21.8) | 1.75 (1.08–2.86) | NA | ||||
| AA | 10 (7.8) | 2.0 (0.0–5.4) | 2.44 (1.06–5.56) | NA | ||||
| Winther-Larsen et al., 2015 [32] | AS-PCR or PCR followed by sequencing | CC | 252 (80.0) | NA | Reference | NA | ||
| CT or TT | 64 (20.0) | NA | 0.73 (0.54–0.97) | NA | ||||
|
| ||||||||
| rs4947492 | Intron variant, g.106268G>A | Zhang et al., 2013 [31] | MassARRAY system | AA | 55 (43.0) | 14.9 (6.9–22.8) | Reference | NA |
| AG | 60 (46.9) | 11.8 (3.6–20.0) | 0.86 (0.53–1.39) | NA | ||||
| GG | 13 (10.1) | 24.6 (NA) | 0.29 (0.10–0.83) | NA | ||||
|
| ||||||||
| rs712829 | 5′ UTR variant, g.5031G>T, -216G>T | Giovannetti et al., 2010 [57] | TaqMan assay | GG | 34 (36.2) | 8.0 (3.0–13.0) | NA | NA |
| GT or TT | 60 (63.8) | 11.6 (5.7–17.5) | NA | NA | ||||
| Jung et al., 2012 [25] | PCR-RFLP or PCR followed by sequencing | GG | 63 (88.7) | 29.5 (17.4–41.7) | NA | NA | ||
| GT | 8 (11.3) | 1.4 (3.7–39.5) | NA | NA | ||||
| Kim et al., 2017 [61] | Taqman PCR and sequencing | GG | 78 (32.0) | NA | Reference | NA | ||
| GT or TT | 162 (68.0) | NA | 0.67 (0.48–0.94) | NA | ||||
| Winther-Larsen et al., 2015 [32] | AS-PCR or PCR followed by sequencing | GG | 134 (42.0) | NA | Reference | NA | ||
| GT or TT | 182 (58.0) | NA | 0.89 (0.70–1.13) | NA | ||||
| Liu et al., 2008 [56] | PCR-RFLP | GG | 34 (37.0) | NA | Reference | NA | ||
| GT or TT | 58 (63.0) | NA | 0.73 (0.45–1.19) | NA | ||||
|
| ||||||||
| rs712830 | 5′ UTR variant, g.5056A>C, -191C/A | Giovannetti et al., 2010 [57] | TaqMan assay | CC | 78 (83.0) | 7.9 (7.0–8.7) | NA | NA |
| CA or AA | 16 (17.0) | 6.0 (2.8–9.2) | NA | NA | ||||
| Kim et al., 2017 [61] | Taqman PCR and sequencing | CC | 195 (81.0) | NA | Reference | NA | ||
| CA or AA | 45 (19.0) | NA | 1.19 (0.80–1.78) | NA | ||||
| Winther-Larsen et al., 2015 [32] | AS-PCR or PCR followed by sequencing | CC | 236 (75.0) | NA | Reference | NA | ||
| CA or AA | 80 (25.0) | NA | 0.95 (0.73–1.25) | NA | ||||
| Liu et al., 2008 [56] | PCR-RFLP | CC | 81 (88.0) | NA | Reference | NA | ||
| CA or AA | 11 (12.0) | NA | 1.09 (0.52–2.29) | NA | ||||
|
| ||||||||
| rs7809028 | Regulatory region variant, g.198953G>A | Zhang et al., 2013 [31] | MassARRAY system | GG | 60 (49.2) | 20.9 (7.4–34.4) | Reference | NA |
| GA | 53 (43.4) | 16.5 (10.2–20.4) | 0.74 (0.45–1.21) | NA | ||||
| AA | 9 (7.4) | 2.0 (1.0–3.1) | 0.52 (0.22–1.21) | NA | ||||
OS: overall survival; HR: hazard ratio; RR: relative risk; NA: not available.