Background
Materials and methods
Study population
DNA extraction and genotyping
H. pylori infection detection
Statistical analysis
Result
Characteristics of the study population
Association between polymorphisms and risk of gastric cancer
Polymorphism | Genotype | Cases, n (%) | Controls, n (%) | OR (95% CI) | OR (95% CI)a | p value |
---|---|---|---|---|---|---|
IL-16 rs4072111 | CC | 334 (69.73) | 345 (71.43) | Reference | Reference | |
TC | 126 (26.30) | 122 (25.26) | 1.07 (0.80,1.43) | 1.01 (0.75,1.36) | 0.970 | |
TT | 19 (3.97) | 16 (3.31) | 1.23 (0.62,2.43) | 1.20 (0.60,2.41) | 0.600 | |
TC/TT | 145 (30.27) | 138 (28.57) | 1.09 (0.82,1.43) | 1.02 (0.77,1.36) | 0.870 | |
Additive model | 1.08 (0.86,1.37) | 1.04 (0.82,1.32) | 0.755 | |||
rs4778889 | TT | 267 (55.74) | 266 (55.07) | Reference | Reference | |
CT | 182 (38.00) | 192 (39.75) | 0.94 (0.73,1.23) | 0.92 (0.70,1.20) | 0.524 | |
CC | 30 (6.26) | 25 (5.18) | 1.20 (0.68,2.09) | 1.19 (0.68,2.10) | 0.542 | |
CT/CC | 212 (44.26) | 217 (44.93) | 0.97 (0.76,1.26) | 0.95 (0.73,0.23) | 0.688 | |
Additive model | 1.01 (0.82,1.25) | 1.00 (0.81,1.23) | 0.965 | |||
rs859 | TT | 129 (26.93) | 124 (25.67) | Reference | Reference | |
CT | 235 (49.06) | 248 (51.35) | 0.91 (0.67,1.24) | 0.88 (0.64,1.20) | 0.406 | |
CC | 115 (24.01) | 111 (22.98) | 1.00 (0.70,1.43) | 0.98 (0.68,1.41) | 0.899 | |
CT/CC | 350 (73.07) | 359 (74.33) | 0.94 (0.70,1.25) | 0.92 (0.68,1.23) | 0.551 | |
Additive model | 1.00 (0.83,1.19) | 0.98 (0.82,1.18) | 0.859 | |||
rs11556218 | TT | 306 (63.88) | 308 (63.77) | Reference | Reference | |
GT | 151 (31.52) | 157 (32.51) | 1.97 (0.74,1.27) | 0.93 (0.71,1.23) | 0.628 | |
GG | 22 (4.59) | 18 (3.73) | 1.23 (0.65,2.34) | 1.29 (0.68,2.48) | 0.439 | |
GT/GG | 173 (36.12) | 175 (36.23) | 1.00 (0.77,1.29) | 0.97 (0.94,1.27) | 0.820 | |
Additive model | 1.02 (0.82,1.28) | 1.01 (0.81,1.27) | 0.913 | |||
rs1131445 | TT | 221 (46.14) | 210 (43.48) | Reference | Reference | |
CT | 211 (44.05) | 222 (45.96) | 0.90 (0.69,1.18) | 0.94 (0.72,1.23) | 0.655 | |
CC | 47 (9.81) | 51 (10.56) | 0.88 (0.57,1.36) | 0.93 (0.59,1.46) | 0.748 | |
CT/CC | 258 (53.86) | 273 (56.52) | 0.90 (0.70,1.16) | 0.93 (0.72,1.21) | 0.592 | |
Additive model | 0.92 (0.76,1.12) | 0.95 (0.78,1.16) | 0.618 | |||
TLR4 rs10759932 | TT | 240 (50.10) | 251 (51.97) | Reference | Reference | |
TC | 191 (39.87) | 196 (40.58) | 1.02 (0.78,1.33) | 1.05 (0.80,1.38) | 0.733 | |
CC | 48 (10.02) | 36 (7.45) | 1.39 (0.87,2.22) | 1.38 (0.86,2.23) | 0.184 | |
TC/CC | 239 (49.90) | 232 (48.03) | 1.08 (0.84,1.39) | 1.10 (0.85,1.42) | 0.481 | |
Additive model | 1.11 (0.91,1.35) | 1.12 (0.92,1.36) | 0.275 | |||
rs1927911 | GG | 171 (35.70) | 175 (36.23) | Reference | Reference | |
GA | 226 (47.18) | 226 (46.79) | 1.02 (0.77,1.35) | 1.04 (0.78,1.38) | 0.801 | |
AA | 82 (17.12) | 82 (16.98) | 1.02 (0.71,1.48) | 0.99 (0.68,1.45) | 0.967 | |
GA/AA | 308 (64.30) | 308 (63.77) | 1.02 (0.79,1.33) | 1.03 (0.79,1.34) | 0.844 | |
Additive model | 1.01 (0.85,1.21) | 1.01 (0.84,1.21) | 0.930 | |||
rs11536889 | GG | 303 (63.26) | 293 (60.66) | Reference | Reference | |
CG | 156 (32.57) | 166 (34.37) | 0.91 (0.69,1.19) | 0.91 (0.69,1.19) | 0.477 | |
CC | 20 (4.18) | 24 (4.97) | 0.81 (0.44,1.49) | 0.76 (0.40,1.43) | 0.392 | |
CG/CC | 176 (36.74) | 190 (39.34) | 0.90 (0.69,1.16) | 0.89 (0.69,1.16) | 0.402 | |
Additive model | 0.90 (0.73,1.13) | 0.90 (0.72,1.12) | 0.355 | |||
TGF-BR1 rs6478974 | TT | 219 (45.72) | 194 (40.17) | Reference | Reference | |
AT | 204 (42.59) | 220 (45.55) | 0.82 (0.63,1.08) | 0.80 (0.61,1.06) | 0.118 | |
AA | 56 (11.69) | 69 (14.29) | 0.72 (0.48,1.08) | 0.68 (0.45,1.02) | 0.063 | |
AT/AA | 260 (54.28) | 289 (59.83) | 0.80 (0.62,1.03) | 0.78 (0.60,1.01) | 0.055 | |
Additive model | 0.84 (0.70,1.01) |
0.82 (0.68,0.99)
|
0.038
| |||
rs334348 | AA | 143 (29.85) | 158 (32.71) | Reference | Reference | |
AG | 221 (46.14) | 240 (49.69) | 1.02 (0.76,1.36) | 1.05 (0.78,1.42) | 0.730 | |
GG | 115 (24.01) | 85 (17.60) | 1.50 (1.04,2.14) |
1.51 (1.05,2.18)
|
0.028
| |
AG/GG | 336 (70.15) | 325 (69.29) | 1.14 (0.87,1.50) | 1.17 (0.89,1.55) | 0.263 | |
Additive model | 1.20 (1.01,1.43) |
1.22 (1.02,1.46)
|
0.032
| |||
rs10512263 | TT | 279 (58.25) | 262 (54.24) | Reference | Reference | |
CT | 178 (37.16) | 187 (38.72) | 0.89 (0.69,1.17) | 0.87 (0.66,1.14) | 0.297 | |
CC | 22 (4.59) | 34 (7.04) | 0.61 (0.35,1.07) |
0.54 (0.31,0.97)
|
0.039
| |
CT/CC | 200 (41.75) | 221 (45.76) | 0.85 (0.66,1.10) | 0.82 (0.63,1.06) | 0.127 | |
Additive model | 0.84 (0.68,1.03) |
0.81 (0.65,1.00)
|
0.047
|
Genotype | Age | Gender | H. pylori infection | |||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
≤ 64 | > 64 | Male | Female | Positive | Negative | |||||||||||||
Ca/Co | OR (95% CI)a | p value | Ca/Co | OR (95% CI)a | p value | Ca/Co | OR (95% CI)a | p value | Ca/Co | OR (95% CI)a | p value | Ca/Co | OR (95% CI)a | p value | Ca/Co | OR (95% CI)a | p value | |
rs6478974 | ||||||||||||||||||
TT | 100/87 | Reference | 119/107 | Reference | 156/134 | Reference | 63/60 | Reference | 120/91 | Reference | 99/103 | Reference | ||||||
AT | 101/113 | 0.76 (0.51,1.13) | 0.175 | 103/107 | 0.85 (0.58,1.25) | 0.412 | 159/170 | 0.80 (0.58,1.10) | 0.164 | 45/50 | 0.81 (0.46,.41) | 0.452 | 108/107 | 0.76 (0.52,1.12) | 0.160 | 96/113 | 0.86 (0.58,1.28) | 0.457 |
AA | 28/30 | 0.76 (0.41,1.40) | 0.374 | 28/39 | 0.61 (0.34,1.07) | 0.082 | 38/54 |
0.55 (0.33,0.90)
|
0.017
| 18/15 | 1.19 (0.55,2.58) | 0.663 | 33/33 | 0.73 (0.41,1.28) | 0.272 | 23/36 | 0.62 (0.34,1.14) | 0.127 |
AT/AA | 129/143 | 0.76 (0.52,1.11) | 0.156 | 131/146 | 0.80 (0.56,1.14) | 0.206 | 197/224 |
0.74 (0.54,1.00)
|
0.049
| 63/65 | 0.89 (0.54,1.48) | 0.658 | 141/140 | 0.75 (0.52,1.08) | 0.125 | 119/149 | 0.81 (0.55,1.17) | 0.260 |
Additive model | 0.83 (0.63,1.10) | 0.199 | 0.81 (0.62,1.04) | 0.100 |
0.76 (0.61,0.95)
|
0.016
| 1.01 (0.70,1.44) | 0.975 | 0.83 (0.64,1.08) | 0.157 | 0.81 (0.62,1.07) | 0.135 | ||||||
rs334348 | ||||||||||||||||||
AA | 72/74 | Reference | 71/84 | Reference | 108/121 | Reference | 35/37 | Reference | 77/83 | Reference | 66/75 | Reference | ||||||
AG | 105/122 | 0.95 (0.62,1.47) | 0.832 | 116/118 | 1.16 (0.77,1.76) | 0.478 | 168/173 | 1.15 (0.81,1.62) | 0.143 | 53/67 | 0.85 (0.46,1.54) | 0.583 | 124/100 | 1.43 (0.94,2.17) | 0.093 | 97/140 | 0.79 (0.51,1.21) | 0.278 |
GG | 52/34 | 1.57 (0.90,2.73) | 0.114 | 63/51 | 1.44 (0.88,2.37) | 0.146 | 77/64 | 1.37 (0.89,2.11) | 0.149 | 38/21 | 1.97 (0.94,4.11) | 0.072 | 60/48 | 0.37 (0.83,2.25) | 0.223 | 55/37 | 1.71 (0.99,2.53) | 0.054 |
AG/GG | 157/156 | 1.09 (0.72,1.63) | 0.694 | 179/169 | 1.26 (0.86,1.85) | 0.245 | 245/237 | 1.20 (0.87,1.66) | 0.269 | 91/88 | 1.10 (0.63,1.92) | 0.745 | 184/148 | 1.40 (0.95,2.06) | 0.088 | 152/177 | 0.98 (0.66,1.47) | 0.927 |
Additive model | 1.21 (0.93,1.59) | 0.161 | 1.22 (0.95,1.56) | 0.113 | 1.17 (0.95,1.45) | 0.141 | 1.36 (0.95,1.94) | 0.096 | 1.19 (0.93,1.53) | 0.166 | 1.25 (0.96,1.64) | 0.097 | ||||||
rs10512263 | ||||||||||||||||||
TT | 130/129 | Reference | 149/133 | Reference | 202/189 | Reference | 77/73 | Reference | 150/127 | Reference | 129/135 | Reference | ||||||
CT | 88/88 | 0.95 (0.64,1.41) | 0.814 | 90/99 | 0.80 (0.55,1.16) | 0.230 | 136/140 | 0.89 (0.65,1.22) | 0.470 | 42/47 | 0.82 (0.48,1.41) | 0.471 | 98/87 | 0.91 (0.62,1.33) | 0.610 | 80/100 | 0.83 (0.56,1.22) | 0.335 |
CC | 11/13 | 0.70 (0.29,1.67) | 0.417 | 11/21 |
0.44 (0.20,0.96)
|
0.040
| 15/29 |
0.41 (0.21,0.81)
|
0.010
| 7/5 | 1.40 (0.42,4.63) | 0.585 | 13/17 | 0.64 (0.29,1.39) | 0.258 | 9/17 | 0.45 (0.19,1.10) | 0.080 |
CT/CC | 99/101 | 0.91 (0.62,1.33) | 0.621 | 101/120 | 0.74 (0.52,1.06) | 0.101 | 151/169 | 0.80 (0.59,1.09) | 0.159 | 49/52 | 0.87 (0.52,1.46) | 0.604 | 111/104 | 0.86 (0.60,1.23) | 0.405 | 89/117 | 0.77 (0.53,1.13) | 0.180 |
Additive model | 0.88 (0.64,1.21) | 0.441 |
0.74 (0.55,0.99)
|
0.040
|
0.76 (0.60,0.98)
|
0.033
| 0.96 (0.63,1.48) | 0.864 | 0.85 (0.63,1.14) | 0.272 | 0.76 (0.56,1.04) | 0.083 |
Genotype | Co | Clinical stage | Tumor site | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
T1–T2 | T3–T4 | Cardiac | Non-cardiac | ||||||||||
Ca | OR (95% CI)a | p value | Ca | OR (95% CI)a | p value | Ca | OR (95% CI)a | p value | Ca | OR (95% CI)a | p value | ||
rs6478974 | |||||||||||||
TT | 194 | 75 | Reference | 144 | Reference | 62 | Reference | 157 | Reference | ||||
AT | 220 | 69 | 0.82 (0.55,1.21) | 0.311 | 135 | 0.79 (0.58,1.08) | 0.140 | 62 | 0.87 (0.58,1.31) | 0.497 | 142 | 0.78 (0.57,1.05) | 0.105 |
AA | 69 | 15 | 0.54 (0.28,1.04) | 0.065 | 41 | 0.76 (0.49,1.20) | 0.238 | 14 | 0.61 (0.32,1.17) | 0.139 | 42 | 0.72 (0.45,1.13) | 0.147 |
AT/AA | 289 | 84 | 0.75 (0.52,1.09) | 0.134 | 176 | 0.79 (0.59,1.05) | 0.109 | 76 | 0.80 (0.54,1.18) | 0.268 | 184 | 0.77 (0.58,1.02) | 0.069 |
Additive model | 0.76 (0.57,1.01) | 0.054 | 0.85 (0.69,1.05) | 0.140 | 0.80 (0.60,1.07) | 0.135 | 0.83 (0.67,1.02) | 0.077 | |||||
rs334348 | |||||||||||||
AA | 158 | 45 | Reference | 98 | Reference | 40 | Reference | 103 | Reference | ||||
AG | 240 | 73 | 1.19 (0.76,1.87) | 0.442 | 148 | 1.01 (0.73,1.41) | 0.937 | 64 | 1.14 (0.73,1.80) | 0.565 | 157 | 1.04 (0.75,1.45) | 0.825 |
GG | 85 | 41 |
1.73 (1.03,2.90)
|
0.039
| 74 | 1.42 (0.94,2.13) | 0.092 | 34 | 1.56 (0.91,2.68) | 0.103 | 81 | 1.48 (0.99,2.21) | 0.055 |
AG/GG | 325 | 114 | 1.31 (0.87,1.99) | 0.196 | 222 | 1.12 (0.82,1.52) | 0.487 | 1.24 (0.81,1.89) | 0.323 | 1.15 (0.85,1.57) | 0.373 | ||
Additive model |
1.33 (1.02,1.73)
|
0.035
| 1.17 (0.96,1.43) | 0.125 | 1.25 (0.95,1.64) | 0.108 | 1.21 (0.99,1.47) | 0.069 | |||||
rs10512263 | |||||||||||||
TT | 262 | 99 | Reference | 180 | Reference | 82 | Reference | 197 | Reference | ||||
CT | 187 | 53 | 0.75 (0.51,1.12) | 0.161 | 125 | 0.93 (0.69,1.25) | 0.620 | 50 | 0.81 (0.54,1.21) | 0.300 | 128 | 0.90 (0.67,1.21) | 0.479 |
CC | 34 | 7 | 0.51 (0.21,1.24) | 0.137 | 15 | 0.59 (0.31,1.13) | 0.113 | 6 | 0.51 (0.20,1.28) | 0.149 | 16 | 0.56 (0.29,1.07) | 0.080 |
CT/CC | 221 | 60 | 0.71 (0.49,1.05) | 0.084 | 140 | 0.88 (0.66,1.17) | 0.366 | 56 | 0.76 (0.51,1.12) | 0.162 | 144 | 0.85 (0.64,1.13) | 0.256 |
Additive model | 0.73 (0.53,1.01) | 0.054 | 0.85 (0.67,1.08) | 0.184 | 0.76 (0.55,1.05) | 0.093 | 0.83 (0.66,1.05) | 0.120 |
Association between polymorphisms and clinical outcome
Genotype | Cases, n | Death, n (%) | Log-rank p-value | HR | HR (95% CI)a | p-value |
---|---|---|---|---|---|---|
rs4072111 | ||||||
CC | 322 | 205 (0.64) | Reference | Reference | ||
TC/TT | 138 | 81 (0.59) | 0.344 | 0.88 (0.68,1.14) | 1.12 (0.86,1.45) | 0.408 |
rs4778889 | ||||||
TT | 256 | 172 (0.67) | Reference | Reference | ||
CT/CC | 204 | 114 (0.56) | 0.028 | 0.77 (0.61,0.97) | 0.84 (0.66,1.06) | 0.146 |
rs11556218 | ||||||
TT | 293 | 192 (0.66) | Reference | Reference | ||
GT/GG | 167 | 94 (0.56) | 0.110 | 0.82 (0.64,1.05) | 0.94 (0.73,1.20) | 0.607 |
rs859 | ||||||
AA | 109 | 68 (0.62) | Reference | Reference | ||
GA/GG | 351 | 218 (0.62) | 0.633 | 1.07 (0.81,1.40) | 1.03 (0.79,1.36) | 0.814 |
rs1131445 | ||||||
TT | 211 | 127 (0.60) | Reference | Reference | ||
CT/CC | 249 | 159 (0.64) | 0.150 | 1.18 (0.94,1.50) | 1.06 (0.84,1.35) | 0.617 |
rs10759932 | ||||||
TT | 231 | 141 (0.61) | Reference | Reference | ||
TC/CC | 229 | 145 (0.63) | 0.563 | 1.07 (0.85,1.35) | 1.07 (0.84,1.35) | 0.588 |
rs1927911 | ||||||
GG | 165 | 95 (0.58) | Reference | Reference | ||
GA/AA | 295 | 191 (0.65) | 0.113 | 1.22 (0.95,1.56) |
1.27 (1.00,1.63)
| 0.054 |
rs11536889 | ||||||
GG | 293 | 181 (0.62) | Reference | Reference | ||
CG/CC | 167 | 105 (0.63) | 0.957 | 1.01 (0.79,1.28) | 0.99 (0.77,1.26) | 0.924 |
rs6478974 | ||||||
TT | 212 | 126 (0.59) | Reference | Reference | ||
TA/AA | 248 | 160 (0.65) | 0.224 | 1.16 (0.92,1.46) | 1.23 (0.98,1.56) | 0.079 |
rs334348 | ||||||
GG | 110 | 64 (0.58) | Reference | Reference | ||
AG/AA | 350 | 222 (0.63) | 0.491 | 1.10 (0.84,1.46) | 1.04 (0.79,1.38) | 0.787 |
rs10512263 | ||||||
TT | 269 | 157 (0.58) | Reference | Reference | ||
CT/CC | 191 | 129 (0.68) | 0.031 |
1.29 (1.02,1.63)
|
1.29 (1.02,1.63)
|
0.031
|
Group | Case, n | Death, n (%) | rs1927911 | rs10512263 | ||||
---|---|---|---|---|---|---|---|---|
GA/AA: GG | HR (95% CI)a | p-value | CT/CC: TT | HR (95% CI)a | P-value | |||
Age | ||||||||
< 64 | 224 | 130 (0.58) |
142/82
|
1.64 (1.13,2.38)
|
0.009
| 97/127 | 1.34 (0.95,1.90) | 0.099 |
≥ 64 | 236 | 156 (0.66) | 153/83 | 1.04 (0.75,1.45) | 0.817 | 94/142 | 1.19 (0.86,1.64) | 0.286 |
Gender | ||||||||
Male | 338 | 214 (0.63) |
216/122
|
1.36 (1.03,1.81)
|
0.033
|
145/193
|
1.43 (1.09,1.87)
|
0.010
|
Female | 122 | 72 (0.64) | 79/43 | 1.08 (0.65,1.80) | 0.754 | 46/76 | 1.26 (0.76,2.08) | 0.365 |
Clinical stage | ||||||||
T1–T2 | 159 | 42 (0.26) | 102/57 | 1.36 (0.70,2.66) | 0.367 |
60/99
|
2.61 (1.40,4.86)
|
0.003
|
T3–T4 | 301 | 244 (0.81) | 193/108 | 1.21 (0.93,1.58) | 0.160 | 131/170 | 1.04 (0.80,1.34) | 0.784 |
Tumor site | ||||||||
Cardiac | 132 | 87 (0.66) | 91/41 | 1.07 (0.67,1.71) | 0.768 | 54/78 | 1.47 (0.94,2.31) | 0.094 |
Non-cardiac | 328 | 199 (0.61) |
204/124
|
1.34 (1.00,1.80)
|
0.050
|
137/191
|
1.36 (1.02,1.80)
|
0.034
|
rs1927911 | rs10512263 | Cases, n | Death, n (%) | Log-rank p value | HR (95% CI)a | p-value |
---|---|---|---|---|---|---|
GG | TT | 100 | 53 (53.00) | 0.018 | Reference | |
GG | CT/CC | 65 | 42 (64.42) | 1.18 (0.79,1.03) | 0.421 | |
GA/AA | TT | 169 | 104 (61.54) | 1.20 (0.86,1.67) | 0.279 | |
GA/AA | CT/CC | 126 | 87 (69.05) |
1.64 (1.17,2.31)
|
0.005
|