Background
Methods
Database searching and screening
Characteristics and quality assessment
Heterogeneity and association test
Publication bias and sensitivity analysis
Results
Process for identifying eligible studies
First author | Year | Country | Race | NOS | SNP | Case | Assay | Control | |||
---|---|---|---|---|---|---|---|---|---|---|---|
AA/AB/BB | Type | AA/AB/BB | Source | HWE | |||||||
Balaji | 2011 | India | Mixed | 8 | rs3813867 | 151/6/0 | HNSCC | TaqMan allelic discrimination | 125/7/0 | PB | Y |
rs2031920 | 151/6/0 | HNSCC | TaqMan allelic discrimination | 125/7/0 | PB | Y | |||||
rs2031920/rs3813867 | 151/6/0 | HNSCC | TaqMan allelic discrimination | 125/7/0 | PB | Y | |||||
Bhat | 2014 | India | Asian | 6 | rs2031920 | 366/148/12 | ESCC | PCR–RFLP | 207/308/11 | HB | N |
Bouchardy | 2000 | France | Caucasian | 7 | rs2031920 | 109/11/1 | HNSCC | PCR–RFLP | 164/8/0 | HB | Y |
Brocic | 2011 | Serbia | Caucasian | 9 | rs2031920 | 105/13/5 | HNSCC | PCR–RFLP | 160/16/1 | PB | Y |
Cao | 2014 | China | Asian | 7 | rs3813867 | 143/44/2 | LSCC | PCR–RFLP | 340/168/18 | HB | Y |
Cury | 2012 | Brazil | Africa | 7 | rs3813867 | 160/141 | HNSCC | PCR–RFLP | 242/361 | PB | Y |
Ferreira | 2006 | Portugal | Caucasian | 7 | rs2031920 | 113/91 | CSCC | PCR–RFLP | 224/111 | PB | Y |
Gajecka | 2005 | Poland | Caucasian | 6 | rs2031920 | 279/9/0 | HNSCC | PCR–RFLP | 305/18/0 | PB | Y |
Gattas | 2006 | Brazil | Africa | 6 | rs3813867 | 90/13/0 | HNSCC | PCR–RFLP | 96/6/0 | HB | Y |
rs3813867 | 31/7/0a | HNSCC | PCR–RFLP | 96/6/0 | HB | Y | |||||
Gonzalez | 1998 | Spain | Caucasian | 6 | rs3813867 | 68/6/1 | HNSCC | PCR–RFLP | 179/21/0 | PB | Y |
Guo | 2012 | China | Asian | 8 | rs2031920 | 195/1252 | HNSCC | PCR–RFLP | 254/662 | PB | NR |
Guo | 2008 | China | Asian | 8 | rs2031920/rs3813867 | 57/16/7 | ESCC | PCR–RFLP | 225/180/75 | PB | N |
Huang | 2000 | China | Asian | 8 | rs2031920 | 10/13/1 | LSCC | PCR–RFLP | 152/101/7 | PB | N |
Le | 1998 | USA | Mixed | 8 | rs2031920 | 56/17/1 | LSCC | PCR–RFLP | 338/102/14 | PB | Y |
Lee | 2006 | Korea | Asian | 6 | rs2031920 | 30/37/6 | LSCC | PCR–RFLP | 90/89/12 | HB | Y |
Li, D | 2005 | South Africa | Mixed | 8 | rs2031920 | 184/5/0 | ESCC | SSCP | 191/7/0 | PB | Y |
rs3813867 | 184/5/0 | ESCC | SSCP | 187/11/0 | PB | Y | |||||
Li | 2008 | China | Asian | 7 | rs2031920/rs3813867 | 39/311 | LSCC | PCR–RFLP | 83/691 | PB | Y |
Li, G | 2005 | USA | Caucasian | 6 | rs3813867 | 684/37/3 | HNSCC | PCR–RFLP | 1137/86/3 | HB | Y |
Li | 2011 | China | Asian | 6 | rs3813867 | 159/67/0 | ESCC | PCR–RFLP | 173/62/11 | HB | Y |
Li | 2000 | China | Asian | 7 | rs2031920 | 40/11/2 | LSCC | PCR–RFLP | 75/57/5 | PB | Y |
Liu | 2007 | China | Asian | 8 | rs2031920 | 34/33/10 | ESCC | PCR–RFLP | 45/29/5 | PB | Y |
Matthias | 2003 | Germany | Caucasian | 6 | rs2031920/rs3813867 | 307/18/1b | HNSCC | PCR–RFLP | 165/10/0 | HB | Y |
rs2031920/rs3813867 | 35/3/0c | HNSCC | PCR–RFLP | 165/10/0 | HB | Y | |||||
Morita | 1997 | Japan | Asian | 8 | rs2031920/rs3813867 | 34/18/1 | ESCC | PCR–RFLP | 85/42/5 | PB | Y |
Neuhaus | 2004 | Germany | Caucasian | 6 | rs2031920 | 304/8/0 | HNSCC | PCR | 282/13/2 | PB | N |
Nishino | 2008 | Japan | Asian | 6 | rs2031920 | 74/44/6 | CSCC | PCR–RFLP | 68/42/7 | PB | Y |
Oyama | 2002 | Japan | Asian | 6 | rs2031920 | 40/8/5 | LSCC | PCR–RFLP | 391/196/25 | PB | Y |
Pandey | 2012 | India | Caucasian | 7 | rs2031920 | 47/31 | HNSCC | PCR–RFLP | 35/151 | PB | NR |
Ruwali | 2010 | India | Asian | 6 | rs2031920 | 327/231 | HNSCC | NR | 343/71 | PB | NR |
Soya | 2008 | India | Asian | 7 | rs2031920/rs3813867 | 394/141 | HNSCC | PCR–RFLP | 212/81 | HB | Y |
Tai | 2010 | China | Asian | 9 | rs2031920 | 184/81/13 | HNSCC | PCR–RFLP | 182/84/12 | PB | Y |
Tan | 2010 | China | Asian | 9 | rs2031920 | 107/31/12 | ESCC | PCR–RFLP | 66/77/7 | PB | N |
Wang | 2012 | China | Asian | 8 | rs3813867 | 156/74/10d | ESCC | Gel-based DNA microarray | 131/94/20 | PB | Y |
rs3813867 | 149/85/8e | ESCC | Gel-based DNA microarray | 109/94/18 | PB | Y | |||||
rs2031920 | 154/76/10d | ESCC | Gel-based DNA microarray | 131/94/20 | PB | Y | |||||
rs2031920 | 141/93/8e | ESCC | Gel-based DNA microarray | 108/95/18 | PB | Y |
The rs2031920 polymorphism
Comparisons | Group | Number (study) | OR | 95% CI | P (association) |
---|---|---|---|---|---|
Allele model (allele T vs. allele C) | All | 18 | 0.84 | 0.67–1.06 | 0.144 |
Asian | 11 | 0.80 | 0.61–1.05 | 0.106 | |
Caucasian | 4 | 1.04 | 0.46–2.37 | 0.929 | |
HNSCC | 6 | 0.99 | 0.62–1.59 | 0.971 | |
ESCC | 6 | 0.67 | 0.48–0.95 | 0.025 | |
LSCC | 5 | 0.94 | 0.67–1.32 | 0.722 | |
PB | 15 | 0.83 | 0.68–1.02 | 0.076 | |
HB | 3 | 1.00 | 0.38–2.58 | 0.994 | |
Y | 14 | 0.92 | 0.75–1.13 | 0.449 | |
N | 4 | 0.60 | 0.37–0.99 | 0.048 | |
Carrier model (carrier T vs. carrier C) | All | 18 | 0.83 | 0.69–1.01 | 0.064 |
Asian | 11 | 0.80 | 0.60–1.00 | 0.053 | |
Caucasian | 4 | 0.99 | 0.49–1.99 | 0.982 | |
HNSCC | 6 | 0.96 | 0.65–1.43 | 0.849 | |
ESCC | 6 | 0.70 | 0.53–0.93 | 0.014 | |
LSCC | 5 | 0.92 | 0.68–1.25 | 0.602 | |
PB | 15 | 0.83 | 0.71–0.98 | 0.027 | |
HB | 3 | 0.98 | 0.44–2.16 | 0.955 | |
Y | 14 | 0.91 | 0.78–1.06 | 0.236 | |
N | 4 | 0.62 | 0.42–0.92 | 0.018 | |
Homozygote model (TT vs. CC) | All | 15 | 0.87 | 0.65–1.15 | 0.324 |
Asian | 11 | 0.83 | 0.62–1.12 | 0.324 | |
Caucasian | 3 | 2.18 | 0.66–7.19 | 0.202 | |
HNSCC | 4 | 1.35 | 0.69–2.62 | 0.379 | |
ESCC | 5 | 0.65 | 0.44–0.96 | 0.029 | |
LSCC | 5 | 1.27 | 0.69–2.33 | 0.440 | |
PB | 12 | 0.85 | 0.62–1.17 | 0.316 | |
HB | 3 | 0.94 | 0.49–1.79 | 0.847 | |
Y | 11 | 0.90 | 0.65–1.24 | 0.522 | |
N | 4 | 0.76 | 0.42–1.38 | 0.371 | |
Heterozygote model (CT vs. CC) | All | 18 | 0.74 | 0.54–1.02 | 0.067 |
Asian | 11 | 0.68 | 0.45–1.02 | 0.064 | |
Caucasian | 4 | 0.93 | 0.51–1.71 | 0.825 | |
HNSCC | 6 | 0.92 | 0.66–1.28 | 0.617 | |
ESCC | 6 | 0.56 | 0.32–0.97 | 0.040 | |
LSCC | 5 | 0.82 | 0.45–1.47 | 0.503 | |
PB | 15 | 0.73 | 0.56–0.96 | 0.024 | |
HB | 3 | 0.85 | 0.23–3.17 | 0.804 | |
Y | 14 | 0.85 | 0.69–1.05 | 0.139 | |
N | 4 | 0.48 | 0.23–1.01 | 0.054 | |
Dominant model (CT + TT vs. CC) | All | 21 | 0.81 | 0.60–1.11 | 0.189 |
Asian | 12 | 0.80 | 0.54–1.19 | 0.263 | |
Caucasian | 6 | 0.85 | 0.42–1.71 | 0.644 | |
HNSCC | 8 | 0.95 | 0.56–1.62 | 0.844 | |
ESCC | 6 | 0.58 | 0.35–0.96 | 0.035 | |
LSCC | 5 | 0.87 | 0.53–1.44 | 0.591 | |
PB | 18 | 0.81 | 0.61–1.07 | 0.138 | |
HB | 3 | 0.89 | 0.24–3.33 | 0.864 | |
Y | 15 | 0.90 | 0.72–1.12 | 0.345 | |
N | 4 | 0.50 | 0.25–0.99 | 0.046 | |
Recessive model (TT vs. CC + CT) | All | 16 | 1.21 | 0.80–1.83 | 0.362 |
Asian | 12 | 1.20 | 0.78–1.84 | 0.402 | |
Caucasian | 3 | 2.11 | 0.23–19.71 | 0.512 | |
HNSCC | 5 | 1.88 | 0.91–3.90 | 0.089 | |
ESCC | 5 | 0.91 | 0.47–1.74 | 0.770 | |
LSCC | 5 | 1.47 | 0.81–2.69 | 0.206 | |
PB | 13 | 1.18 | 0.72–1.94 | 0.514 | |
HB | 3 | 1.24 | 0.66–2.34 | 0.497 | |
Y | 11 | 1.05 | 0.65–1.71 | 0.829 | |
N | 4 | 1.26 | 0.70–2.28 | 0.438 |
The rs3813867 polymorphism
Comparisons | Group | Number (study) | OR | 95% CI | P (association) |
---|---|---|---|---|---|
Allele model (allele C vs. allele G) | All | 10 | 0.72 | 0.63–0.83 | < 0.001 |
Asian | 4 | 0.67 | 0.57–0.78 | < 0.001 | |
HNSCC | 5 | 0.97 | 0.73–1.30 | 0.863 | |
ESCC | 4 | 0.68 | 0.57–0.82 | < 0.001 | |
PB | 5 | 0.65 | 0.53–0.79 | < 0.001 | |
HB | 5 | 0.80 | 0.66–0.97 | 0.021 | |
Y | 10 | 0.72 | 0.63–0.83 | < 0.001 | |
Carrier model (carrier C vs. carrier G) | All | 10 | 0.79 | 0.68–0.92 | 0.002 |
Asian | 4 | 0.75 | 0.63–0.90 | 0.001 | |
HNSCC | 5 | 0.94 | 0.70–1.27 | 0.698 | |
ESCC | 4 | 0.77 | 0.63–0.93 | 0.008 | |
PB | 5 | 0.72 | 0.58–0.89 | 0.003 | |
HB | 5 | 0.85 | 0.70–1.05 | 0.133 | |
Y | 10 | 0.79 | 0.68–0.92 | 0.002 | |
Homozygote model (CC vs. GG) | All | 6 | 0.38 | 0.24–0.61 | < 0.001 |
Asian | 4 | 0.30 | 0.18–0.50 | < 0.001 | |
HNSCC | 2 | 2.34 | 0.58–9.34 | 0.230 | |
ESCC | 3 | 0.30 | 0.17–0.53 | < 0.001 | |
PB | 3 | 0.43 | 0.24–0.75 | 0.003 | |
HB | 3 | 0.30 | 0.12–0.74 | 0.009 | |
Y | 6 | 0.38 | 0.24–0.61 | < 0.001 | |
Heterozygote model (GC vs. GG) | All | 10 | 0.82 | 0.63–107 | 0.150 |
Asian | 4 | 0.75 | 0.56–0.99 | 0.045 | |
HNSCC | 5 | 1.15 | 0.62–2.16 | 0.657 | |
ESCC | 4 | 0.76 | 0.54–1.07 | 0.116 | |
PB | 5 | 0.66 | 0.51–0.84 | 0.001 | |
HB | 5 | 1.09 | 0.67–1.76 | 0.730 | |
Y | 10 | 0.82 | 0.63–107 | 0.150 | |
Dominant model (GC + CC vs. GG) | All | 11 | 0.76 | 0.60–0.97 | 0.024 |
Asian | 4 | 0.68 | 0.54–0.86 | 0.002 | |
HNSCC | 6 | 1.01 | 0.62–1.65 | 0.961 | |
ESCC | 4 | 0.70 | 0.53–0.92 | 0.011 | |
PB | 6 | 0.62 | 0.50–0.77 | < 0.001 | |
HB | 5 | 1.03 | 0.65–1.62 | 0.916 | |
Y | 11 | 0.76 | 0.60–0.97 | 0.024 | |
Recessive model (CC vs. GG + GC) | All | 6 | 0.43 | 0.27–0.68 | < 0.001 |
Asian | 4 | 0.34 | 0.20–0.57 | < 0.001 | |
HNSCC | 2 | 2.39 | 0.60–9.53 | 0.218 | |
ESCC | 3 | 0.35 | 0.20–0.60 | < 0.001 | |
PB | 3 | 0.49 | 0.28–0.86 | 0.013 | |
HB | 3 | 0.31 | 0.13–0.77 | 0.011 | |
Y | 6 | 0.43 | 0.27–0.68 | < 0.001 |
The rs2031920/rs3813867 haplotype
Comparisons | Group | Number (study) | OR | 95% CI | P (association) |
---|---|---|---|---|---|
Allele c2 vs. allele c1 | All | 5 | 0.65 | 0.49–0.86 | 0.003 |
HNSCC | 3 | 1.01 | 0.57–1.78 | 0.977 | |
PB | 3 | 0.57 | 0.42–0.79 | 0.001 | |
Y | 4 | 0.98 | 0.65–1.46 | 0.913 | |
Carrier c2 vs. carrier c1 | All | 5 | 0.73 | 0.53–1.00 | 0.047 |
HNSCC | 3 | 0.98 | 0.55–1.75 | 0.945 | |
PB | 3 | 0.65 | 0.45–0.93 | 0.019 | |
Y | 4 | 0.98 | 0.64–1.50 | 0.938 | |
c2c2 vs. c1c1 | All | 3 | 0.41 | 0.20–0.86 | 0.018 |
c1c2 vs. c1c1 | All | 5 | 0.75 | 0.43–1.30 | 0.309 |
HNSCC | 3 | 0.96 | 0.53–1.71 | 0.877 | |
PB | 3 | 0.63 | 0.29–1.35 | 0.231 | |
Y | 4 | 1.00 | 0.64–1.56 | 0.990 | |
c1c2 + c2c2 vs. c1c1 | All | 7 | 0.72 | 0.55–0.94 | 0.016 |
HNSCC | 4 | 0.97 | 0.59–1.57 | 0.892 | |
PB | 4 | 0.64 | 0.47–0.87 | 0.005 | |
Y | 6 | 0.97 | 0.70–1.35 | 0.871 | |
c2c2 vs. c1c1 + c1c2 | All | 3 | 0.55 | 0.26–1.13 | 0.103 |
Heterogeneity evaluation
SNP | Comparisons | I2 (%) | P (heterogeneity) | F/R | P (Begg’s test) | P (Egger’s test) |
---|---|---|---|---|---|---|
rs2031920 (C/T) | Allele T vs. allele C | 77.2 | < 0.001 | R | 0.649 | 0.054 |
Carrier T vs. carrier C | 58.9 | 0.001 | R | 0.449 | 0.077 | |
TT vs. CC | 38.3 | 0.066 | F | 0.276 | 0.242 | |
CT vs. CC | 82.1 | < 0.001 | R | 0.544 | 0.544 | |
CT + TT vs. CC | 83.1 | < 0.001 | R | 0.608 | 0.037 | |
TT vs. CC + CT | 57.4 | 0.002 | R | 0.685 | 0.207 | |
rs3813867 (G/C) | Allele C vs. allele G | 46.1 | 0.054 | F | 0.074 | 0.072 |
Carrier C vs. carrier G | 28.4 | 0.183 | F | 0.107 | 0.150 | |
CC vs. GG | 45.4 | 0.103 | F | 0.707 | 0.651 | |
GC vs. GG | 52.4 | 0.026 | R | 0.107 | 0.230 | |
GC + CC vs. GG | 47.3 | 0.041 | R | 0.062 | 0.150 | |
CC vs. GG + GC | 43.6 | 0.115 | F | 1.000 | 0.732 | |
rs2031920 + rs3813867 (c1/c2) | Allele c2 vs. allele c1 | 49.8 | 0.093 | F | 1.000 | 0.184 |
Carrier c2 vs. carrier c1 | 15.5 | 0.316 | F | 0.806 | 0.245 | |
c2c2 vs. c1c1 | 0.0 | 0.671 | F | 0.296 | 0.269 | |
c1c2 vs. c1c1 | 53.1 | 0.074 | R | 0.806 | 0.327 | |
c1c2 + c2c2 vs. c1c1 | 46.3 | 0.083 | F | 0.764 | 0.227 | |
c2c2 vs. c1c1 + c1c2 | 0.0 | 0.792 | F | 0.296 | 0.501 |