Copyright
©The Author(s) 2015.
World J Gastroenterol. Apr 14, 2015; 21(14): 4310-4322
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4310
Published online Apr 14, 2015. doi: 10.3748/wjg.v21.i14.4310
Table 1 Demographic and clinical characteristics of hepatocellular carcinoma patients
Variable | Our cohort | Hong Kong cohort | ||
n | % | n | % | |
Total | 214 | 100 | 401 | 100 |
Age (yr) | ||||
≤ 55 | 108 | 50.5 | NA | NA |
> 55 | 106 | 49.5 | NA | NA |
Gender | ||||
Male | 176 | 82.2 | 322 | 80.3 |
Female | 38 | 17.8 | 79 | 19.7 |
Smoking behavior | ||||
Yes | 70 | 32.7 | 223 | 55.6 |
No | 144 | 67.3 | 178 | 44.4 |
Cirrhosis | ||||
Present | 126 | 58.9 | 229 | 57.1 |
Absent | 88 | 41.1 | 172 | 42.9 |
Child-Pugh score | ||||
A | 172 | 80.4 | 390 | 97.3 |
B | 42 | 19.6 | 11 | 2.7 |
AFP level (ng/mL) | ||||
< 200 | 100 | 46.7 | NA | NA |
≥ 200 | 114 | 53.3 | NA | NA |
Tumor size | ||||
< 5 cm | 102 | 47.7 | NA | NA |
≥ 5 cm | 112 | 52.3 | NA | NA |
TNM stage | ||||
I + II | 119 | 55.6 | 177 | 44.1 |
III | 95 | 44.4 | 224 | 55.9 |
Outcome | ||||
Dead | 111 | 51.9 | 272 | 67.8 |
Alive | 103 | 48.1 | 129 | 32.2 |
Table 2 Summarized information of selected tagging SNPs in GST genes
Gene | Tagging SNPs | bp position | Ref SNP alleles | MAF_CHB |
GSTA1 | rs6917150 | Chr 6: 52760414 | T/C | 0.338 |
GSTA4 | rs385636 | Chr 6: 52948896 | A/G | 0.174 |
GSTM2 | rs638820 | Chr 1: 110011429 | T/C | 0.344 |
GSTM3 | rs1109138 | Chr 1: 110079472 | G/A | 0.167 |
rs7483 | Chr 1: 110081224 | A/G | 0.244 | |
GSTO1 | rs2282326 | Chr 10: 106010388 | A/C | 0.244 |
rs17116779 | Chr 10: 106021185 | G/A | 0.078 | |
GSTO2 | rs156699 | Chr 10: 106043631 | T/C | 0.222 |
rs7085725 | Chr 10: 106050199 | T/C | 0.122 | |
rs157077 | Chr 10: 106027884 | A/G | 0.378 | |
GSTP1 | rs4147581 | Chr 11: 67108161 | G/C | 0.273 |
rs2370141 | Chr 11: 67105105 | A/G | 0.181 |
Table 3 Associations between polymorphisms of tagging SNPs in GST genes and overall survival in hepatocellular carcinoma patients
Gene | Tagging SNP | Genotype | Outcome, n (%) | HR (95%CI) | P value | |
Dead | Alive | |||||
GSTA1 | rs6917150 | WW | 48 (51.6) | 45 (48.4) | 1 (ref) | |
WV + VV | 63 (52.1) | 58 (47.9) | 1.01 (0.69-1.48) | 0.961 | ||
GSTA4 | rs385636 | WW | 82 (55.4) | 66 (44.6) | 1 (ref) | |
WV + VV | 29 (43.9) | 37 (56.1) | 0.71 (0.46-1.09) | 0.117 | ||
GSTM2 | rs638820 | WW | 42 (51.9) | 39 (48.1) | 1 (ref) | |
WV + VV | 69 (51.9) | 64 (48.1) | 1.13 (0.77-1.67) | 0.526 | ||
GSTM3 | rs1109138 | WW | 85 (54.1) | 72 (45.9) | 1 (ref) | |
WV + VV | 26 (45.6) | 31 (54.4) | 0.81 (0.52-1.26) | 0.353 | ||
rs7483 | WW | 63 (56.2) | 49 (43.8) | 1 (ref) | ||
WV + VV | 48 (47.1) | 54 (52.9) | 0.94 (0.64-1.38) | 0.760 | ||
GSTO1 | rs2282326 | WW | 60 (56.1) | 47 (43.9) | 1 (ref) | |
WV + VV | 51 (47.7) | 56 (52.3) | 0.92 (0.63-1.35) | 0.675 | ||
rs17116779 | WW | 99 (51.0) | 95 (49.0) | 1 (ref) | ||
WV + VV | 12 (60.0) | 8 (40.0) | 0.95 (0.52-1.75) | 0.869 | ||
GSTO2 | rs156699 | WW | 64 (50.0) | 64 (50.0) | 1 (ref) | |
WV + VV | 47 (54.7) | 39 (45.3) | 1.10 (0.75-1.62) | 0.612 | ||
rs7085725 | WW | 81 (46.0) | 95 (54.0) | 1 (ref) | ||
WV + VV | 30 (78.9) | 8 (21.1) | 1.60 (1.03-2.47)a | 0.035a | ||
rs157077 | WW | 50 (58.1) | 36 (41.9) | 1 (ref) | ||
WV + VV | 61 (47.7) | 67 (52.3) | 0.78 (0.54-1.14) | 0.198 | ||
GSTP1 | rs4147581 | WW | 57 (55.3) | 46 (44.7) | 1 (ref) | |
WV + VV | 54 (48.6) | 57 (51.4) | 0.68 (0.46-0.99)a | 0.042a | ||
rs2370141 | WW | 74 (52.1) | 68 (47.9) | 1 (ref) | ||
WV + VV | 37 (51.4) | 35 (48.6) | 0.90 (0.61-1.34) | 0.597 |
Table 4 Stratified analysis on the association between GSTO2: rs7085725 and GSTP1: rs4147581 genotype and overall survival of hepatocellular carcinoma patients
Variable | GSTO2: rs7085725 | GSTP1: rs4147581 | ||||||
Dead/Alive | HR (95%CI) | P value | Dead/Alive | HR (95%CI) | P value | |||
WW | WV + VV | WW | WV + VV | |||||
Age (yr) | ||||||||
≤ 55 | 32/52 | 19/5 | 1.86a (1.02-3.38) | 0.044a | 28/25 | 23/32 | 0.52a (0.30-0.92) | 0.024a |
> 55 | 49/43 | 11/3 | 1.71 (0.89-3.31) | 0.110 | 29/21 | 31/25 | 0.92 (0.55-1.54) | 0.755 |
Gender | ||||||||
Male | 62/83 | 26/5 | 1.83a (1.14-2.94) | 0.013a | 44/38 | 44/50 | 0.64a (0.42-0.99) | 0.042a |
Female | 19/12 | 4/3 | 0.76 (0.22-2.64) | 0.663 | 13/8 | 10/7 | 1.06 (0.45-2.50) | 0.902 |
Smoking behavior | ||||||||
No | 52/67 | 19/6 | 1.35 (0.78-2.37) | 0.287 | 35/26 | 36/47 | 0.58a (0.36-0.93) | 0.024a |
Yes | 29/28 | 11/2 | 2.59a (1.27-5.27) | 0.009a | 22/20 | 18/10 | 1.06 (0.56-1.99) | 0.870 |
Cirrhosis | ||||||||
Absent | 41/30 | 12/5 | 1.21 (0.62-2.35) | 0.579 | 23/17 | 30/18 | 0.91 (0.52-1.59) | 0.746 |
Present | 40/65 | 18/3 | 2.00a (1.11-3.59) | 0.020a | 34/29 | 24/39 | 0.50a (0.29-0.85) | 0.011a |
Child-Pugh score | ||||||||
A | 61/87 | 17/7 | 2.28a (1.32-3.93) | 0.003a | 39/44 | 39/50 | 0.83 (0.53-1.30) | 0.422 |
B | 20/8 | 13/1 | 0.97 (0.47-2.03) | 0.940 | 18/2 | 15/7 | 0.45a (0.22-0.90) | 0.024a |
AFP level (ng/mL) | ||||||||
< 200 | 39/40 | 14/7 | 1.09 (0.57-2.11) | 0.793 | 26/17 | 27/30 | 0.51a (0.29-0.89) | 0.018a |
≥ 200 | 42/55 | 16/1 | 2.40a (1.34-4.29) | 0.003a | 31/29 | 27/27 | 0.85 (0.51-1.44) | 0.552 |
Tumor size | ||||||||
< 5 cm | 37/50 | 10/5 | 1.51 (0.74-3.06) | 0.254 | 23/26 | 24/29 | 0.77 (0.43-1.38) | 0.379 |
≥ 5 cm | 44/45 | 20/3 | 1.59 (0.90-2.80) | 0.109 | 34/20 | 30/28 | 0.60a (0.37-1.00) | 0.048 |
TNM stage | ||||||||
I + II | 44/60 | 11/4 | 1.24 (0.61-2.53) | 0.555 | 27/26 | 28/38 | 0.64 (0.37-1.10) | 0.104 |
III | 37/35 | 19/4 | 1.66 (0.94-2.93) | 0.081 | 30/20 | 26/19 | 0.75 (0.43-1.30) | 0.311 |
Table 5 Cumulative effects of unfavorable genotypes on overall survival of hepatocellular carcinoma patients
Group (number of unfavorable genotypes1) | Death/Total | HR (95%CI) | P value |
In all patients | |||
Group 1 (0) | 44/95 | 1 (ref) | |
Group 2 (1) | 47/97 | 1.08 (0.71-1.63) | 0.730 |
Group 3 (2) | 20/22 | 1.70a (1.30-2.22) | < 0.001a |
P for trend | 0.004a | ||
In patients with age ≤ 55 | |||
Group 1 (0) | 18/47 | 1 (ref) | |
Group 2 (1) | 26/45 | 1.01 (0.52-1.95) | 0.975 |
Group 3 (2) | 14/16 | 2.00a (1.40-3.86) | < 0.001a |
P for trend | 0.003a | ||
In patients with male gender | |||
Group 1 (0) | 36/82 | 1 (ref) | |
Group 2 (1) | 34/75 | 0.97 (0.60-1.56) | 0.898 |
Group 3 (2) | 18/19 | 1.94a (1.45-2.59) | < 0.001a |
P for trend | 0.002a | ||
In patients with cirrhosis | |||
Group 1 (0) | 20/56 | 1 (ref) | |
Group 2 (1) | 24/56 | 1.29 (0.71-2.35) | 0.410 |
Group 3 (2) | 14/14 | 1.97a (1.39-2.79) | < 0.001a |
P for trend | 0.001a |
Table 6 Modulating effects of smoking on hepatocellular carcinoma overall survival by GSTO2: rs7085725 or GSTP1: rs4147581 genotypes
SNP and variables | Death/total | HR (95%CI) | P value |
In patients with WW genotype of GSTO2: rs7085725 | |||
Smoking behavior | |||
No smoking | 52/119 | 1 (ref) | |
Smoking | 29/57 | 1.04 (0.82-1.31) | 0.757 |
Smoking quantity (packs-year)1 | |||
0 | 52/119 | 1 (ref) | |
> 0 and < 20 | 20/45 | 1.06 (0.82-1.37) | 0.667 |
≥ 20 | 9/12 | 0.99 (0.76-1.30) | 0.956 |
In patients with WV + VV genotypes of GSTO2: rs7085725 | |||
Smoking behavior | |||
No smoking | 19/25 | 1 (ref) | |
Smoking | 11/33 | 1.52 (1.02-2.26)a | 0.042a |
Smoking quantity (packs-year)1 | |||
0 | 19/25 | 1 (ref) | |
> 0 and < 20 | 9/11 | 1.42 (0.93-2.16) | 0.106 |
≥ 20 | 2/2 | 2.07 (1.13-3.76) | 0.018a |
In patients with WW genotype of GSTP1: rs4147581 | |||
Smoking behavior | |||
No smoking | 35/61 | 1 (ref) | |
Smoking | 22/42 | 0.95 (0.72-1.24) | 0.697 |
Smoking quantity (packs-year)1 | |||
0 | 35/61 | 1 (ref) | |
> 0 and < 20 | 15/33 | 0.97 (0.71-1.31) | 0.824 |
≥ 20 | 7/9 | 0.95 (0.71-1.28) | 0.754 |
In patients with WV + VV genotypes of GSTP1: rs4147581 | |||
Smoking behavior | |||
No smoking | 36/83 | 1 (ref) | |
Smoking | 18/28 | 1.27 (0.95-1.69) | 0.101 |
Smoking quantity (packs-year)1 | |||
0 | 36/83 | 1 (ref) | |
> 0 and < 20 | 14/23 | 1.27 (0.93-1.74) | 0.128 |
≥ 20 | 4/5 | 1.16 (0.81-1.66) | 0.426 |
- Citation: Qu K, Liu SS, Wang ZX, Huang ZC, Liu SN, Chang HL, Xu XS, Lin T, Dong YF, Liu C. Polymorphisms of glutathione S-transferase genes and survival of resected hepatocellular carcinoma patients. World J Gastroenterol 2015; 21(14): 4310-4322
- URL: https://www.wjgnet.com/1007-9327/full/v21/i14/4310.htm
- DOI: https://dx.doi.org/10.3748/wjg.v21.i14.4310