Background
Methods
Search strategy and selection criteria
Data extraction
Statistical analysis
Results
Study characteristics
Study | Year | Country | Ethnicity | Case No. | Genotyping method | Stage | Treatment Response (Genotype distribution) | Outcome | SNPs of XRCC1 | HWE | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
XRCC1 Arg399Gln | XRCC1 Arg194Trp | ||||||||||||||||||||
CR + PR | SD + PD | CR + PR | SD + PD | ||||||||||||||||||
GG | GA | AA | GG | GA | AA | CC | CT | TT | CC | CT | TT | ||||||||||
Peng [17] | 2014 | China | Asian | 235 | PCR-CTTP | IIIA-IV | 40 | 41 | 3 | 71 | 74 | 6 | − | − | − | − | − | − | TR/OS/PFS | Arg399Gln | <0.005 |
Zhang [23] | 2014 | China | Asian | 375 | Sequenom MassARRAY | IIIA-IV | 49 | 54 | 24 | 125 | 94 | 29 | 60 | 44 | 23 | 118 | 90 | 41 | TR/OS/PFS | Arg194Trp Arg399Gln | <0.05 |
Lee [24] | 2013 | S. Korea | Asian | 382 | Sequenome mass spectrometry-based genotyping assay | III-IV | 110 | 64 | 5 | 100 | 75 | 16 | − | − | − | − | − | − | TR/OS | Arg399Gln | >0.05 |
Tiseo [30] | 2013 | Italy | Caucasian | 93 | TaqMan | IIIB-IV | 14 | 4 | 27 | 2 | − | − | − | − | − | − | TR/OS | Arg399Gln | − | ||
Zhao [26] | 2013 | China | Asian | 147 | TaqMan allelic discrimination assay | IIIA-IV | 21 | 24 | 8 | 56 | 31 | 5 | 32 | 20 | 1 | 51 | 35 | 6 | TR/OS/PFS | Arg194Trp Arg399Gln | >0.05 |
Li [18] | 2012 | China | Asian | 89 | PCR-RFLP | IIIA-IV | 20 | 6 | 24 | 39 | − | − | − | − | − | − | TR | Arg399Gln | − | ||
Liao 1[20] | 2012 | Taiwan | Asian | 62 | SNPstream UHT | IIIB-IV | 9 | 9 | 1 | 17 | 22 | 4 | − | − | − | − | − | − | TR/OS | Arg399Gln | >0.05 |
Liao 2[20] | 2012 | Taiwan | Asian | 45 | SNPstream UHT | IIIB-IV | − | − | − | − | − | − | − | − | − | − | − | − | OS | Arg399Gln | >0.05 |
Joerger [22] | 2012 | Netherlands | Caucasian | 131 | BigDye Terminator Cycle Sequencing Ready Reaction Kit | IIIB-IV | 17 | 18 | 5 | 34 | 45 | 12 | − | − | − | − | − | − | TR/OS/PFS | Arg399Gln | >0.05 |
Xu [14] | 2011 | China | Asian | 130 | PCR-RFLP | IIIB-IV | 30 | 14 | 0 | 36 | 40 | 10 | 12 | 14 | 18 | 42 | 26 | 18 | TR | Arg194Trp Arg399Gln | >0.05 |
Zhou [21] | 2011 | China | Asian | 111 | PCR-RFLP | IV | 29 | 6 | 42 | 34 | − | − | − | − | − | − | TR/TTP | Arg399Gln | − | ||
Yuan [31] | 2010 | China | Asian | 199 | PCR-RFLP | IIIA-IV |
−
|
−
|
−
|
−
|
−
|
−
| − | − | − | − | − | − | OS/PFS | Arg194Trp Arg399Gln | − |
Hong [13] | 2009 | China | Asian | 164 | PCR-RFLP | III-IV | 26 | 28 | 3 | 44 | 53 | 10 | 19 | 31 | 7 | 54 | 42 | 11 | TR | Arg194Trp Arg399Gln | >0.05 |
Kalikaki [19] | 2009 | Greece | Caucasian | 119 | PCR-RFLP | IIIA-IV | 11 | 26 | 21 | 60 | − | − | − | − | − | − | TR/OS | Arg399Gln | − | ||
Sun [27] | 2009 | China | Asian | 87 | 3D DNA microarray | IV | 14 | 8 | 1 | 39 | 22 | 3 | 8 | 18 | 5 | 31 | 19 | 6 | TR | Arg194Trp Arg399Gln | >0.05 |
Yao [29] | 2009 | China | Asian | 102 | PCR-RFLP | IIIB-IV | 13 | 9 | 32 | 48 | − | − | − | − | − | − | TR/OS | Arg399Gln | − | ||
De las Penas R. [25] | 2006 | Spain | Caucasian | 135 | allelic discrimination assay | IIIB-IV | - | − | − | − | − | − | − | − | − | − | − | − | OS | Arg399Gln | − |
Yuan [16] | 2006 | China | Asian | 200 | PCR-RFLP | Advanced | 24 | 38 | 10 | 69 | 46 | 13 | TR | Arg194Trp | >0.05 | ||||||
Gurubhagavatula [28] | 2004 | USA | Caucasian | 103 | PCR-RFLP | IIIA-IV | - | − | − | − | − | − | − | − | − | − | − | − | OS | Arg399Gln | - |
Wang [15] | 2004 | China | Asian | 105 | PCR-RFLP | IIIB-IV | 22 | 9 | 2 | 31 | 33 | 8 | 11 | 19 | 3 | 43 | 18 | 11 | TR | Arg194Trp Arg399Gln | >0.05 |
Meta-analysis results
XRCC1 194 polymorphism
Objective response
XRCC1 | Objective response | Overall survival | Progression-free survival | ||||||
---|---|---|---|---|---|---|---|---|---|
Studies(refs.) | Pooled OR | Ph /I
2(%) | Studies(refs.) | Pooled HR | Ph /I
2(%) | Studies(refs.) | Pooled HR | Ph /I
2(%) | |
Arg194Trp
| |||||||||
ArgArg vs. TrpTrp | |||||||||
All | 7 [13–16, 23, 26, 27] |
0.64(0.44-0.91)
| 0.19/31.1 | 3 [23, 26, 31] | 1.19(0.73–1.65) | 0.92/0.0 | 3 [23, 26, 31] | 1.28(0.74–1.82) | 0.92/0.0 |
Sample size>100 | 6 [13–16, 23, 26] |
0.67(0.46-0.97)
| 0.17/35.4 | 3 [23, 26, 31] | 1.19(0.73–1.65) | 0.92/0.0 | 3 [23, 26, 31] | 1.28(0.74–1.82) | 0.92/0.0 |
Year ≥ 2009 | 5 [13, 14, 23, 26, 27] |
0.65(0.44-0.99)
| 0.09/49.8 | 3 [23, 26, 31] | 1.19(0.73–1.65) | 0.92/0.0 | 3 [23, 26, 31] | 1.28(0.74–1.82) | 0.92/0.0 |
TrpArg vs. TrpTrp | |||||||||
All | 7 [13–16, 23, 26, 27] | 1.05(0.73–1.51) | 0.35/10.8 | - | - | - | - | - | - |
Sample size>100 | 6 [13–16, 23, 26] | 1.04(0.71–1.52) | 0.24/25.4 | - | - | - | - | - | - |
Year ≥ 2009 | 5 [13, 14, 23, 26, 27] | 0.91(0.60–1.39) | 0.56/0.0 | - | - | - | - | - | - |
ArgArg + TrpArg vs. TrpTrp | |||||||||
All | 7 [13–16, 23, 26, 27] | 0.79(0.56–1.11) | 0.32/13.9 | 1 [26] | - | - | 1 [26] | - | - |
Sample size>100 | 6 [13–16, 23, 26] | 0.80(0.57–1.14) | 0.23/27.1 | 1 ([26]) | - | - | 1 [26] | - | - |
Year ≥ 2009 | 5 [13, 14, 23, 26, 27] | 0.75(0.51–1.10) | 0.26/24.6 | 1 ([26]) | - | - | 1 [26] | - | - |
ArgArg vs. TrpArg + TrpTrp | |||||||||
All | 7 [13–16, 23, 26, 27] |
0.55(0.36-0.84)
| 0.01/63.0 | 3 [23, 26, 31] | 1.07(0.79–1.35) | 0.79/0.0 | 3 [23, 26, 31] | 0.94(0.72–1.17) | 0.648/0.0 |
Sample size>100 | 6 [13–16, 23, 26] |
0.60(0.39-0.92)
| 0.02/62.7 | 3 [23, 26, 31] | 1.07(0.79–1.35) | 0.79/0.0 | 3 [23, 26, 31] | 0.94(0.72–1.17) | 0.648/0.0 |
Year ≥ 2009 | 5 [13, 14, 23, 26, 27] | 0.63(0.37–1.05) | 0.02/65.9 | 3 [23, 26, 31] | 1.07(0.79–1.35) | 0.79/0.0 | 3 [23, 26, 31] | 0.94(0.72–1.17) | 0.648/0.0 |
Arg399Gln
| |||||||||
GlnGln vs. ArgArg | |||||||||
All | 10 [13–15, 17, 20, 22–24, 26, 27] | 0.77(0.38–1.57) | 0.005/62.0 | 7 [17, 19, 22–24, 28, 31] | 1.15(0.61–1.69) | 0.006/66.6 | 5 [17, 22, 23, 26, 31] |
0.72(0.48-0.97)
| 0.136/42.9 |
Sample size>100 | 8 [13–15, 17, 22–24, 26] | 0.77(0.35–1.73) | 0.002/69.9 | 7 [17, 19, 22–24, 28, 31] | 1.15(0.61–1.69) | 0.006/66.6 | 5 [17, 22, 23, 26, 31] |
0.72(0.48-0.97)
| 0.136/42.9 |
Asian | 9 [13–15, 17, 20, 23, 24, 26, 27] | 0.75(0.33–1.68) | 0.003/66.1 | 4 [17, 23, 24, 31] | 0.86(0.41–1.30) | 0.052/61.2 | 4 [17, 23, 26, 31] |
0.67(0.40-0.94)
| 0.106/51.0 |
Caucasian | 1 [22] | - | - | 3 [19, 22, 28] |
2.29(1.25-3.33)
| 0.423/0.0 | 1 [22] | - | - |
Year ≥ 2009 | 9 [13, 14, 17, 22–24, 26, 27] | 0.83(0.39–1.77) | 0.005/63.5 | 6 [17, 19, 22–24, 31] | 1.06(0.54–1.57) | 0.011/66.2 | 5 [17, 22, 23, 26, 31] |
0.72(0.48-0.97)
| 0.136/42.9 |
GlnArg vs. ArgArg | |||||||||
All | 10 [13–15, 17, 20, 22–24, 26, 27] | 0.90(0.67–1.21) | 0.053/46.2 | 7 [17, 19, 23–25, 28, 31] | 0.93(0.68–1.18) | 0.003/69.3 | 4 [17, 23, 26, 31] | 0.96(0.79–1.14) | 0.416/0.0 |
Sample size>100 | 8 [13–15, 17, 22–24, 26] | 0.89(0.63–1.26) | 0.02/57.8 | 7 [17, 19, 23–25, 28, 31] | 0.93(0.68–1.18) | 0.003/69.3 | 4 [17, 23, 26, 31] | 0.96(0.79–1.14) | 0.416/0.0 |
Asian | 9 [13–15, 17, 20, 23, 24, 26, 27] | 0.90(0.65–1.25) | 0.035/51.8 | 4 [17, 23, 24, 31] | 0.91(0.56–1.27) | 0.003/78.1 | 4 [17, 23, 26, 31] | 0.96(0.79–1.14) | 0.416/0.0 |
Caucasian | 1 [22] | - | - | 3 [19, 25, 28] | 1.01(0.51–1.51) | 0.057/65.2 | - | - | - |
Year ≥ 2009 | 9 [13, 14, 17, 22–24, 26, 27] | 0.97(0.79–1.20) | 0.112/38.4 | 5 [17, 19, 23, 24, 31] | 0.97(0.64–1.31) | 0.003/74.7 | 4 [17, 23, 26, 31] | 0.96(0.79–1.14) | 0.416/0.0 |
GlnGln + GlnArg vs. ArgArg | |||||||||
All | 13 [13–15, 17–24, 26, 27] | 0.72(0.50–1.04) | 0.000/70.9 | 6 [17, 19, 20, 23, 26, 31] | 0.73(0.50–1.05) | 0.001/72.5 | 4 [17, 23, 26, 31] | 0.94(0.77–1.10) | 0.274/22.8 |
Sample size>100 | 10 [13–15, 17, 19, 21–24, 26] | 0.78(0.53–1.16) | 0.000/72.5 | 5 [17, 19, 23, 26, 31] | 0.85(0.55–1.15) | 0.02/65.9 | 4 [17, 23, 26, 31] | 0.94(0.77–1.10) | 0.274/22.8 |
Asian | 11 [13–15, 17, 18, 20, 21, 23, 24, 26, 27] | 0.70(0.46–1.07) | 0.000/75.7 | 5 [17, 20, 23, 26, 31] |
0.65(0.43-0.98)
| 0.003/71.7 | 4 [17, 23, 26, 31] | 0.94(0.77–1.10) | 0.274/22.8 |
Caucasian | 2 [19, 22] | 0.82(0.46–1.44) | 0.966/0.0 | 1 [19] | - | - | - | - | - |
Year ≥ 2009 | 12 [13, 14, 17–24, 26, 27] | 0.93(0.65–1.34) | 0.004/64.3 | 6 [17, 19, 20, 23, 26, 31] | 0.73(0.50–1.05) | 0.001/72.5 | 4 [17, 23, 26, 31] | 0.94(0.77–1.10) | 0.274/22.8 |
GlnGln vs. GlnArg + ArgArg | |||||||||
All | 12 [13–15, 17, 20, 22–24, 26, 27, 29, 30] | 0.85(0.50–1.45) | 0.028/49.0 | 5 [19, 24, 26, 29, 30] | 1.19(0.53–1.84) | 0.01/68.9 | 2 [26, 30] | 0.94(0.37–1.52) | 0.435/0.0 |
Sample size>100 | 9 [13–15, 17, 22–24, 26, 29] | 0.78(0.43–1.41) | 0.015/58.0 | 4 [19, 24, 26, 29] |
1.44(1.01-1.88)
| 0.686/0.0 | 1 [26] | - | - |
Asian | 10 [13–15, 17, 20, 23, 24, 26, 27, 29] | 0.75(0.41–1.37) | 0.023/53.4 | 3 [24, 26, 29] | 1.40(0.96–1.84) | 0.999/0.0 | 1 [26] | - | - |
Caucasian | 2 [22, 30] | 1.58(0.42–5.98) | 0.194/40.6 | 2 [19, 30] | 1.43(−1.05–3.91) | 0.058/72.1 | 1 [30] | - | - |
Year ≥ 2009 | 11 [13, 14, 17, 20, 22–24, 26, 27, 29, 30] | 0.87(0.47–1.62) | 0.038/51.0 | 5 [19, 24, 26, 29, 30] | 1.19(0.53–1.84) | 0.01/68.9 | 2 [26, 30] | 0.94(0.37–1.52) | 0.435/0.0 |