Table 1.
Statistically significant variants from meta‐analyses, false‐positive report probabilities (FPRP), and cumulative epidemiological evidence
| PMID | Gene (variant) | Cancer type | Year | Comparison | Ethnicity | OR (95% CI) | Publication bias/heterogeneity | I 2 (%) | No. of studies | Cases/control | Number of test allele or genotype (calculated value according to MAF) | Maf | Venice Criteriaa | Venice Grade | Power Or of 1.5 | FPRP values at prior probability of 0.001 at power OR of 1.5 | Cumulative epidemiological evidenceb | Ref. |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CYP1A1 | ||||||||||||||||||
| 25048966 | CYP1A1 exon7 (rs1048943) | EC | 2014 | Dominant | Diverse | 1.49 (1.33‐1.66) | P = 0.815/0.036 | 38.30% | 18 | 6165 (2552/3613) | 2863 | 0.2281 | ABA | Moderate | 0.548 | 0.000 | Strong | 37 |
| EC | 2014 | Dominant | Asian | 1.48 (1.33‐1.66) | P = 0.925/0.026 | 44.20% | 15 | 5431 (2381/3050) | 2703 | 0.2598 | ABA | Moderate | 0.591 | 0.000 | Strong | 37 | ||
| EC | 2014 | Dominant | Caucasian | 1.50 (0.87‐2.59) | P = 0.537/0.254 | 25.20% | 3 | 734 (171/563) | Na | Na | Na | Na | Na | Na | Na | 37 | ||
| CYP1A1 | ||||||||||||||||||
| 25886559 | CYP1A1 (rs4646903) | EC | 2015 | Additive | Asian | 1.25 (1.04‐1.51) | P = 0.550/0.000 | 67.10% | 12 | 3161 (1359/1802) | 2645 | 0.4001 | ACA | Weak | 0.971 | 0.955 | Weak | 38 |
| ESCC | 2015 | Additive | Asian | 1.17 (1.04‐1.32) | 0.544c/0.055c | 47.4%c | 9 | 2384 (1027/1357) | 1897 | 0.3868 | ABA | Moderate | 1.000 | 0.915 | Weak | 38 | ||
| ERCC2 751 | ||||||||||||||||||
| 25748732 | ERCC2 (rs13181) | EC | 2015 | Dominant | Diverse | 1.30 (1.07‐1.57) | P = No/<0.05 | 80.00% | 21 | 14 832 (6581/8251) | 5570 | 0.2424 | ACA | Weak | 0.931 | 0.873 | Weak | 39 |
| EC | 2015 | Dominant | Asian | 1.27 (1.04‐1.56) | P = No/<0.05 | 66.7%c | 12 | 7265 (3338/3927) | 1778 | 0.1179 | ACA | Weak | 0.944 | 0.960 | Weak | 39 | ||
| ESCC | 2015 | Dominant | diveres | 1.27 (1.04‐1.55) | P = 0.229/0.000c | 66.7%c | 13 | 8111 (3351/4760) | 2385 | 0.1673 | ACA | Weak | 0.949 | 0.952 | Weak | 39 | ||
| EADC | 2015 | Dominant | diveres | 1.16 (0.87‐1.55) | Na | Na | 7 | 5122 (1726/3396) | Na | Na | Na | Na | Na | Na | Na | 39 | ||
| 21667112 | ERCC2 (rs1052559) | EC | 2012 | Homozygous | Asian | 2.45 (1.10‐5.44) | P = 0.83/0.355 | 7.7%c | 4 | 2352 (1093/1259) | 28 | 0.0436 | CAA | Weak | 0.114 | 0.996 | Weak | 40 |
| EADC | 2012 | Homozygous | diveres | 1.26 (1.02‐1.56) | P = 0.277/0.054 | 54%c | 6 | 4341 (1281/3060) | 593 | 0.3565 | BCA | Weak | 0.945 | 0.973 | Weak | 40 | ||
| ESCC | 2012 | Homozygous | diveres | 1.32 (0.85‐2.06) | Na | Na | 6 | 3185 (1294/1281) | Na | Na | Na | Na | Na | Na | Na | 40 | ||
| ERCC2 | ||||||||||||||||||
| 25209371 | ERCC2 (rs238406) | ESCC | 2014 | Dominant | Asian | 1.24 (1.04‐1.49) | P = No/0.017 | Na | 1 | 2257 (1126/1131) | 1534 | 0.424 | AXA | Na | 0.979 | 0.957 | Na | 41 |
| Fas | ||||||||||||||||||
| 24598538 | Fas (rs2234767) | EC | 2014 | Recessive | Diverse | 1.58 (1.16‐2.13) | P=>0.05/0.089 | 58.70% | 3 | 2660 (1126/1534) | Na (0‐490) | 0.1841d | XCA | Na | 0.367 | 0.880 | Na | 42 |
| GSTP1 | ||||||||||||||||||
| 25280543 | GSTP1 (rs1695) | EC | 2015 | Additive | Caucasian | 1.146 (1.031‐1.275) | P = 0.901/0.175 | 30.40% | 9 | 3289 (1198/2019) | 2333 | 0.3479 | ABCe | Weak | 1.000 | 0.925 | Weak | 43 |
| ESCC | 2015 | Additive | Caucasian | 1.041 (0.956‐1.134) | Na | Na | 15 | Na | Na | Na | Na | Na | Na | Na | Na | 43 | ||
| EADC | 2015 | Additive | Caucasian | 1.096 (0.971‐1.237) | Na | Na | 10 | Na | Na | Na | Na | Na | Na | Na | Na | 43 | ||
| HOTAIR | ||||||||||||||||||
| 27791260 | HOTAIR (rs920778) | ESCC | 2017 | Recessive | Asian | 2.525 (1.921‐3.320) | P=>0.396/0.368 | 0.1%c | 3 | 4221 (2071/2150) | 259 | 0.2105 | BAA | Moderate | 0.000 | 0.000 | Strong | 44 |
| IL‐18 | ||||||||||||||||||
| 26214646 | IL‐18 (−607C>A) | EC | 2015 | Dominant | Diverse | 1.29 (1.00‐1.66) | P = 0.088/0.70 | 0.00%c | 2 | 1749 (1305/444) | 1175 | 0.4561 | AAA | Strong | 0.879 | 0.982 | Moderate | 45 |
| MMP1 | ||||||||||||||||||
| 23644699 | MMP1 (rs1799750) | EC | 2013 | Dominant | Diverse | 1.47 (1.18‐1.82) | P = 0.127/0.78 | 0.00% | 3 | 1936 (856/1080) | 1457 | 0.5181 | AAA | Strong | 0.574 | 0.415 | Moderate | 46 |
| MnSOD | ||||||||||||||||||
| 23679296 | MnSOD (rs4880) | EC | 2013 | Dominant | Na | 1.74 (1.36‐2.22) | P = 0.61/0.64 | 0.00% | 4 | 1529 (620/909) | Na (628‐1256) | 0.4107d | XAA | Na | 0.116 | 0.067 | Na | 47 |
| MTHFR C677T | ||||||||||||||||||
| 24606463 | MTHFR (rs1801133) | EC | 2014 | Additive | Asian | 1.19 (1.06‐1.34) | P = 0.667/<0.001 | Na | 14 | 6633 (2808/3825) | 6491 | 0.4567 | AXA | Na | 1.000 | 0.803 | Na | 48 |
| NAT2 | ||||||||||||||||||
| 24595082 | NAT2 (rapid/slow) | ESCC | 2013 | slow vs rapid | Asian | 1.35 (1.03‐1.77) | P = 0.805/0.093 | 49.70% | 5 | 1534 (441/1093) | 402 | 0.118 | BBA | Moderate | 0.777 | 0.975 | Weak | 49 |
| hOGG1 | ||||||||||||||||||
| 23909557 | hOGG1 (rs1052133) | EC | 2013 | Recessive | diveres | 1.40 (1.12‐1.74) | P = 0.140/0.176 | 27.40% | 12 | 5984 (2363/3621) | 586 | 0.2813 | BBA | Moderate | 0.733 | 0.767 | Weak | 50 |
| EC | 2013 | Recessive | Asian | 1.51 (1.15‐1.96) | P = 0.140/0.22 | 29.00% | 6 | 2461 (1123/1338) | 408 | 0.3961 | BBA | Moderate | 0.48 | 0.803 | Weak | 50 | ||
| ESCC | 2013 | Recessive | diveres | 1.86 (1.36‐2.53) | P = 0.140/0.73 | 0.00% | 3 | 1271 (589/682) | 200 | 0.3512 | BAA | Moderate | 0.085 | 0.474 | Weak | 50 | ||
| EADC | 2013 | Recessive | Caucasian | 1.08 (0.69‐1.67) | Na | Na | 3 | 2611 (1189/1422) | Na | Na | Na | Na | Na | Na | Na | 50 | ||
| TNF‐α | ||||||||||||||||||
| 27821804 | TNF‐α (rs1800629) | ESCC | 2016 | Dominant | Diverse | 1.19 (1.00‐1.41) | P = No/0.405 | 3.30% | 8 | 4469 (1144/3325) | 1297 | 0.1582 | AAA | Strong | 0.996 | 0.978 | Moderate | 51 |
| PLCE1 | ||||||||||||||||||
| 25422186 | PLCE1 (rs2274223) | EC | 2014 | Dominant | Diverse | 1.30 (1.16‐1.46) | P = No/0.0003 | 68.00% | 12 | 22 935 (9912/13 023) | Na (6846‐13 692) | 0.2985d | ABA | Moderate | 0.992 | 0.009 | Strong | 52 |
| EC | 2014 | Dominant | Asian | 1.39 (1.24‐1.57) | P = No/0.009 | 61.00% | 10 | 19 263 (8737/10 526) | Na (5750‐11 500) | 0.2985d | ABA | Moderate | 0.89 | 0.000 | Strong | 52 | ||
| STK15 T>A | ||||||||||||||||||
| 25452806 | STK15 (rs2273535) | EC | 2015 | Recessive | Asian | 1.19 (1.03‐1.38) | P = 0.835/0.24 | 26.00% | 6 | 3725 (1767/1958) | 1260 | 0.5523 | ABA | Moderate | 0.999 | 0.955 | Weak | 53 |
| C20orf54 | ||||||||||||||||||
| 26154995 | C20orf54 (rs13042395) | ESCC | 2015 | Additive | Diverse | 0.95 (0.90‐0.99) | P = 0.604/0.33 | 13.00% | 7 | 88 324 (29 922/58 402) | Na (19 855) | 0.1124d | AAA | Strong | 1.000 | 0.937 | Moderate | 54 |
| CASP8 −652 6N | ||||||||||||||||||
| 28915630 | CASP8 −652 6 N (rs3834129) | EC | 2017 | Additive | Asian | 0.81 (0.72‐0.92) | P = 0.002/0.712 | 0.00%c | 3 | 2608 (1412/1196) | 1338 | 0.3020 | AAC | Weak | 0.999 | 0.542 | Weak | 55 |
| CYP2E1 | ||||||||||||||||||
| 23226753 | CYP2E1 (RSqI/PstI) | EC | 2012 | Additive | Asian | 0.64 (0.50‐0.81) | P = Na/<0.01 | 80.00% | 17 | 4226 (1663/4266) | 2279 | 0.3016 | ACX | Na | 0.367 | 0.358 | Na | 56 |
| Hsa‐mir | ||||||||||||||||||
| 25433484 | Hsa‐mir‐499 (rs3746444) | EC | 2014 | Additive | Asian | 0.80 (0.66‐0.98) | P = >0.05/0.75 | 0.00%c | 2 | 1358 (669/689) | 498 | 0.2017 | BAA | Moderate | 0.961 | 0.97 | Weak | 57 |
| MicroRNA 34 | ||||||||||||||||||
| 28415817 | MicroRNA (rs4938723) | ESCC | 2017 | Homozygous | Asian | 0.787 (0.638‐0.972) | P = 0.622/0.345 | 9.50% | 4 | 4650 (2226/2424) | 433 | 0.3245 | BAA | Moderate | 0.938 | 0.965 | Weak | 58 |
| MicroRNA 124 | ||||||||||||||||||
| 26171202 | MicroRNA‐124 (rs531564) | ESCC | 2015 | Additive | Asian | 0.87 (0.77‐0.98) | P = No/0.69 | 0.00% | 3 | 4077 (1964/2113) | 1257 | 0.1621 | AAA | Strong | 1.000 | 0.956 | Moderate | 59 |
| MMP2 | ||||||||||||||||||
| 23644699 | MMP2 (rs243865) | EC | 2013 | Dominant | Asian | 0.67 (0.55‐0.80) | P = 0.072/0.59 | 0.00% | 3 | 2781 (1050/1731) | 668 | 0.1416 | BAA | Moderate | 0.522 | 0.018 | Strong | 60 |
| SLC52A3 | ||||||||||||||||||
| 27600099 | SLC52A3 (rs13042395) | EC | 2016 | Recessive | Diverse | 0.84 (0.76‐0.93) | P = 0.357/0.738 | 0.00% | 11 | 26 956 (10 027/16 929) | 2009 | 0.3592 | AAA | Strong | 1.000 | 0.44 | Moderate | 61 |
| ADH1B | ||||||||||||||||||
| 27450204 | ADH1B (rs1229984) | EC | 2016 | Additive | Diverse | 0.67 (0.59‐0.76) | P = No/<0.00001 | 87.00% | 20 | 23 148 (9158/13 990) | 30 676 | 0.6983 | ACA | Weak | 0.531 | 0.000 | Moderate | 62 |
| EC | 2016 | Additive | Asian | 0.66 (0.57‐0.75) | P = No/<0.00001 | 88.00% | 18 | 22 038 (8687/13 351) | 30 595 | 0.7299 | ACA | Weak | 0.439 | 0.000 | Moderate | 62 | ||
| ALDH2 | ||||||||||||||||||
| 25848305 | ALDH2 (rs671) | EC | 2015 | Homozygous | Diverse | 0.69 (0.48‐0.98) | P = 0.682/<0.001 | 74.80% | 31 | 24 707 (8510/16 197) | 1439 | 0.2446 | ACA | Weak | 0.576 | 0.985 | Weak | 63 |
| EC | 2015 | Homozygous | Asian | 0.68 (0.60‐0.79)c | P = 0.682/0.000c | 74.3%c | 30 | 23 481 (8130/15 351) | 1429 | 0.2573 | ACA | Weak | 0.602 | 0.001 | Moderate | 63 | ||
| CCND1 | ||||||||||||||||||
| 24944806 | CCND1 (rs603965) | EC | 2014 | Recessive | Diverse | 1.33 (1.03‐1.73) | P < 0.001/0.000 | 72.10% | 11 | 5343 (2111/3232) | 1471 | 0.5203 | ACC | Weak | 0.815 | 0.976 | Weak | 64 |
| EC | 2014 | Recessive | Asian | 1.22 (0.93‐1.60) | P < 0.001/0.0228 | 30.70% | 4 | Na | Na | Na | Na | Na | Na | Na | Na | 64 | ||
| EC | 2014 | Recessive | Caucasian | 1.44 (0.97‐2.14) | P < 0.001/0.000 | 80.70% | 7 | Na | Na | Na | Na | Na | Na | Na | Na | 64 | ||
| ESCC | 2014 | Recessive | diveres | 1.28 (0.93‐1.75) | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | 64 | ||
| EADC | 2014 | Recessive | Caucasian | 1.59 (0.69‐3.70) | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | 64 | ||
| COX‐2 | ||||||||||||||||||
| 21304218 | COX‐2 (rs20417) | EC | 2011 | Additive | Diverse | 1.45 (1.23‐1.71) | P = 0.922/0.003 | 76.00% | 4 | 3779 (1562/2217 ) | 638 | 0.0753 | BCA | Weak | 0.656 | 0.015 | Moderate | 65 |
| EC | 2011 | Additive | Asian | 1.71 (1.37‐2.17) | P = 0.922/Na | Na | 2 | 2686 (1200/1486 ) | 307 | 0.0451 | BXA | Na | 0.141 | 0.067 | Na | 65 | ||
| EGF | ||||||||||||||||||
| 23403233 | EGF (rs4444903) | EC | 2013 | Additive | Diverse | 1.38 (1.20‐1.59) | P = 0.476/0.997 | 0.00% | 3 | 1713 (779/934) | 1659 | 0.4534 | AAA | Strong | 0.876 | 0.009 | Strong | 66 |
| ERCC2 Asp312Asn | ||||||||||||||||||
| 25356096 | ERCC2 (rs1799793) | EC | 2014 | Dominant | Diverse | 1.14 (1.03‐1.27) | P = 0.096/1.00 | 0.00% | 15 | 9940 (3928/6012) | 2981 | 0.1865 | AACe | Weak | 1.000 | 0.946 | Weak | 67 |
| EC | 2014 | Dominant | diveres | 1.12 (0.99‐1.27) | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | 67 | ||
| EC | 2014 | Dominant | diveres | 1.20 (0.99‐1.47) | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | 67 | ||
| GSTM1 | ||||||||||||||||||
| 26855551 | GSTM1 (null/present) | EC | 2016 | Additive | Diverse | 1.33 (1.12‐1.57) | P = 0.0873/<0.000001 | 77.00% | 37 | 11 949 (4572/7377) | 5478 | 0.2197 | ACA | Weak | 0.922 | 0.449 | Weak | 68 |
| EC | 2016 | Additive | Asian | 1.53 (1.26‐1.86) | P = 0.0873/0.000001 | 77.2%c | 27 | 8406 (3336/5070) | 3814 | 0.2099 | ACA | Weak | 0.421 | 0.045 | Moderate | 68 | ||
| GSTT1 | ||||||||||||||||||
| 23244092 | GSTT1 (null/present) | EC | 2012 | Additive | Asian | 1.26 (1.05‐1.52) | P = 0.270/0.04 | 42.70% | 15 | 3842 (1626/2216) | 1686 | 0.2128 | ABA | Moderate | 0.966 | 0.942 | Weak | 69 |
| MDM2 | ||||||||||||||||||
| 24844868 | MDM2 (rs2279744) | EC | 2015 | Additive | Diverse | 0.88 (0.81‐0.96) | P = 0.83/0.263 | 22.80% | 6 | 4915 (1899/3016) | 4762 | 0.4741 | AAA | Strong | 1.000 | 0.799 | Moderate | 70 |
| EC | 2015 | Homozygous | Asian | 0.7 (0.58‐0.84) | P = 0.94/0.539 | 0.00% | 5 | 4150 (1059/2562) | 1076 | 0.4881 | AAA | Strong | 0.7 | 0.152 | Strong | 70 | ||
| MTHFR A1298C | ||||||||||||||||||
| 23679298 | MTHFR (rs1801131) | EC | 2013 | Recessive | Diverse | 1.843 (1.414‐2.402) | P = 0.801/0.435 | 0.00% | 6 | 3693 (1302/2391) | 246 | 0.2388 | BAA | Moderate | 0.064 | 0.087 | Moderate | 71 |
| EC | 2013 | Recessive | Asian | 3.997 (1.614‐9.900) | P = 0.801/0.409 | 0.00% | 4 | 1652 (598/1054) | 20 | 0.1456 | CAA | Weak | 0.017 | 0.994 | Weak | 71 | ||
| EC | 2013 | Recessive | Caucasian | 1.693 (1.280‐2.240) | P = 0.801/0.936 | 0.00% | 2 | 2037 (704/1333) | 226 | 0.3132 | BAA | Moderate | 0.198 | 0.534 | Weak | 71 | ||
| ESCC | 2013 | Recessive | diveres | 2.57 (1.76‐3.76) | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | 71 | ||
| EADC | 2013 | Recessive | diveres | 1.47 (1.07‐2.01) | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | Na | 71 | ||
| NQO1 607C>T | ||||||||||||||||||
| 28203294 | NQO1 (rs1800566) | EC | 2017 | Additive | Diverse | 1.13 (1.01‐1.26) | P = >0.05/0.000 | 74.40% | 13 | 5385 (2357/3028) | Na (3110) | 0.2889d | ACCe | Weak | 1.000 | 0.965 | Weak | 72 |
| TP53 | ||||||||||||||||||
| 23844939 | TP53 (rs1042522) | EC | 2013 | Additive | Diverse | 1.146 (1.106‐1.293) | P = 0.481/<0.001 | 70.10% | 14 | 11 492 (4184/7308) | 11 550 | 0.4698 | ACCe | Weak | 1.000 | 0.964 | Weak | 73 |
| EC | 2013 | Additive | Asian | 1.194 (1.031‐1.384) | P = 0.499/<0.001 | 70.40% | 11 | 7614 (2317/5297) | 6714 | 0.4188 | ACA | Weak | 0.999 | 0.949 | Weak | 73 | ||
| XRCC1 Arg194Trp | ||||||||||||||||||
| 23543084 | XRCC1 (rs1799782) | EC | 2013 | Recessive | Asian | 1.332 (1.093‐1.624) | P = 0.902/0.074c | 42.30% | 10 | 5290 (1946/3344) | 457 | 0.2929 | BBA | Moderate | 0.88 | 0.839 | Weak | 74 |
| ESCC | 2013 | Recessive | Asian | 1.43 (1.16‐1.75)c | P = 0.872/0.315c | 14.3%c | 9 | 5068 (1840/3228) | 429 | 0.2893 | BAA | Moderate | 0.679 | 0.432 | Weak | 74 | ||
Na, Not available; No significant publication bias/heterogeneity was not found, diversee: two or more ethnicities were reported in the meta‐analysis.
a
Venice Criteria grades are evidence of amount, replication of the association, and protection from bias.
b
Cumulative epidemiological evidence as graded by combination of results from Venice Creteria and FPRP.
c
The information is calculated according to the data provided in the article since the article did not present (such as I 2,OR, publication bias and heterogeneity).
d
The MAF is obtained from dbSNP database.
e
The grade of C is given because the OR value is less than 1.15 and the association is not replicated by GWAS or GWAS meta‐analysis.