Background
Materials and methods
Patients and clinical information
Genotyping
Statistical analysis
Results
Identification of SNPs in the promoter region of the H19 gene
The correlation of H19 rs4930101, rs11042170, rs2735970 with colorectal cancer risk
Genotypes | Controls number (%)a | Cases number (%) |
P
b
| Adjusted OR (95% CI)b |
---|---|---|---|---|
rs4930101 (G/T) | ||||
TT | 56 (10.09) | 30 (5.24) | 1.00 | |
GT | 222 (40.00) | 228 (39.86) |
0.007
|
1.92 (1.19–3.10)
|
GG | 277 (49.91) | 314 (54.90) |
0.001
|
2.12 (1.32–3.39)
|
GT/GG | 499 (89.91) | 542 (94.76) |
0.002
|
2.03 (1.28–3.21)
|
T allele | 334 (30.09) | 288 (25.17) | 1.00 | |
G allele | 776 (69.91) | 856 (74.83) |
0.009
|
1.28 (1.06–1.54)
|
rs2735970 (G/A) | ||||
AA | 228 (41.08) | 174 (30.42) | 1.00 | |
GA | 242 (43.60) | 302 (52.80) |
0.001
|
1.64 (1.26–2.12)
|
GG | 85 (15.32) | 96 (16.78) |
0.029
|
1.48 (1.04–2.11)
|
GA/GG | 327 (58.92) | 398 (69.58) |
0.001
|
1.60 (1.25–2.04)
|
A allele | 698 (62.88) | 650 (56.82) | ||
G allele | 412 (37.12) | 494 (43.18) |
0.003
|
1.29 (1.09–1.52)
|
rs11042170 (G/A) | ||||
AA | 60 (10.81) | 35 (6.12) | 1.00 | |
GA | 226 (40.72) | 223 (38.99) |
0.023
|
1.69 (1.07–2.67)
|
GG | 269 (48.47) | 314 (54.90) |
0.002
|
2.00 (1.28–3.13)
|
GA/GG | 495 (89.19) | 537 (93.88) |
0.005
|
1.86 (1.20–2.87)
|
A allele | 346 (31.17) | 293 (25.61) | 1.00 | |
G allele | 764 (68.83) | 851 (74.39) |
0.003
|
1.32 (1.09–1.58)
|
Combined effect of risk genotypesc | ||||
0 | 36 (6.49) | 8 (1.40) | 1.00 | |
1 | 162 (29.19) | 127 (22.20) |
0.0012
|
3.53 (1.58–7.86)
|
2 | 133 (23.96) | 298 (52.10) | < 0.0001 |
10.08 (4.56–22.28)
|
3 | 224 (40.36) | 139 (24.30) |
0.0087
|
2.79 (1.26–6.18)
|
≤ 1 | 36 (6.49) | 8 (1.40) | 1.00 | |
> 1 | 519 (93.61) | 564 (98.60) | < 0.0001 |
6.48 (2.97–14.15)
|
The interaction between H19 promoter SNPs with environmental factors and clinical variables
rs4930101 | rs2735970 | rs11042170 | Combined genotypes | Weight | Smoking | History | |
---|---|---|---|---|---|---|---|
rs4930101 | 0.055 | < 0.0001 | < 0.0001 | 0.154 | 0.380 | 0.714 | |
rs2735970 | 0.055 | < 0.0001 | < 0.0001 | 0.102 | 0.292 | 0.541 | |
rs11042170 | < 0.0001 |
0.049
| < 0.0001 | 0.754 | 0.099 | 0.085 | |
Combined genotypes | < 0.0001 | < 0.0001 | < 0.0001 | 0.160 | 0.066 |
0.028
| |
Weight | 0.154 | 0.102 | 0.754 | 0.160 | 0.811 | 0.793 | |
Smoking | 0.380 | 0.292 | 0.099 | 0.066 | 0.811 |
0.010
| |
History | 0.714 | 0.541 | 0.085 |
0.028
| 0.793 |
0.010
|
Prognostic markers evaluation of H19 rs4930101, rs11042170, rs2735970 in advanced CRC patients
Stratification | DFS | OS | ||||
---|---|---|---|---|---|---|
Adjusted HR | 95% CIb |
P
a
| Adjusted HR | 95% CIb |
P
a
| |
Body weight, kg | ||||||
rs4930101GG vs. GT/TT | 0.97 | 0.51–1.85 | 0.924 | 1.04 | 0.25–4.35 | 0.955 |
rs2375970AA vs. GA/GG | 0.87 | 0.48–1.59 | 0.658 | 1.64 | 0.49–5.56 | 0.423 |
rs11042170 AA vs. GA/GG | 1.26 | 0.87–1.83 | 0.215 | 1.67 | 0.81–3.45 | 0.168 |
Combined genotypes ≤ 1 vs. > 1 | 1.18 | 0.79–1.76 | 0.421 | 1.79 | 1.09–2.94 |
0.002
|
Smoking | ||||||
rs4930101GG vs. GT/TT | 0.84 | 0.53–1.31 | 0.434 | 1.56 | 0.96–2.54 | 0.073 |
rs2375970AA vs. GA/GG | 1.01 | 0.62–1.63 | 0.975 | 1.40 | 0.86–2.26 | 0.075 |
rs11042170 AA vs. GA/GG | 1.33 | 1.00–1.75 | 0.047 | 0.76 | 0.43–1.32 | 0.325 |
Combined genotypes ≤ 1 vs. > 1 | 2.58 | 1.89–3.53 |
0.001
| 2.64 | 1.84–3.88 |
0.008
|
First-degree family history of cancer | ||||||
rs4930101GG vs. GT/TT | 0.82 | 0.53–1.27 | 0.368 | 1.19 | 0.42–3.32 | 0.742 |
rs2375970AA vs. GA/GG | 1.02 | 0.63–1.64 | 0.952 | 1.40 | 0.50–3.92 | 0.523 |
rs11042170 AA vs. GA/GG | 1.23 | 0.94–1.62 | 0.139 | 1.63 | 0.90–2.93 | 0.105 |
Combined genotypes ≤ 1 vs. > 1 | 1.22 | 0.90–1.65 | 0.203 | 2.75 | 1.17–6.60 |
0.006
|
High-order interactions with CRC prognosis by MDR analysis
Best interaction models | DFS | OS | ||||
---|---|---|---|---|---|---|
Cross-validation consistency |
P
a
| Training odds ratio | Cross-validation consistency |
P
a
| Training odds ratio | |
1 | 81/100 | 0.0579 | 1.38 (0.99–1.92) | 83/100 | 0.0317 | 1.82 (1.05–3.15) |
1,2 | 65/100 | 0.0023 | 1.69 (1.21–2.38) | 95/100 | 0.0032 | 2.27 (1.30–3.95) |
1,2,3 | 100/100 | < 0.0001 | 2.24 (1.59–3.17) | 64/100 | 0.0001 | 3.08 (1.69–5.61) |
1,2,3,4 | 100/100 | < 0.0001 | 2.69 (1.91–3.78) | 47/100 | < 0.0001 | 4.92 (2.51–9.62) |
1,2,3,4,5 | 100/100 | < 0.0001 | 3.71 (2.61–5.26) | 98/100 | < 0.0001 | 14.30 (5.32–38.44) |
1,2,3,4,5,6 | 93/100 | < 0.0001 | 5.08 (3.55–7.27) | 90/100 | < 0.0001 | 27.10 (8.79–83.54) |
1,2,3,4,5,6,7 | 61/100 | < 0.0001 | 8.33 (5.63–12.33) | 92/100 | < 0.0001 | 71.88 (17.19–300.58) |
1,2,3,4,5,6,7,8 | 100/100 | < 0.0001 | 14.44 (9.40–22.16) | 100/100 | < 0.0001 | ∞ |
1,2,3,4,5,6,7,8,9 | 54/100 | < 0.0001 | 23.49 (14.80–37.26) | 100/100 | < 0.0001 | ∞ |
1,2,3,4,5,6,7,8,9,10 | 100/100 | < 0.0001 | 47.27 (27.59–81.01) | 100/100 | < 0.0001 | ∞ |
1,2,3,4,5,6,7,8,9,10,11 | 100/100 | < 0.0001 | 85.18 (45.85–158.23) | 100/100 | < 0.0001 | ∞ |
1,2,3,4,5,6,7,8,9,10,11,12
| 100/100 | < 0.0001 |
85.17 (45.84–158.0)
| 99/100 | < 0.0001 | ∞ |