char = A;code = 65
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = g;code = 103
char = l;code = 108
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = P;code = 80
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = T;code = 84
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = M;code = 77
char = 1;code = 49
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = .;code = 46
result sql = Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer.
Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer.
char = <;code = 60
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char = B;code = 66
char = A;code = 65
char = C;code = 67
char = K;code = 75
char = G;code = 71
char = R;code = 82
char = O;code = 79
char = U;code = 85
char = N;code = 78
char = D;code = 68
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = M;code = 77
char = e;code = 101
char = m;code = 109
char = b;code = 98
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = l;code = 108
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = S;code = 83
char = -;code = 45
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = );code = 41
char = ;code = 32
char = s;code = 115
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char = p;code = 112
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char = r;code = 114
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = c;code = 99
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char = a;code = 97
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char = i;code = 105
char = s;code = 115
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = T;code = 84
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char = e;code = 101
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char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
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char = e;code = 101
char = s;code = 115
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char = a;code = 97
char = t;code = 116
char = t;code = 116
char = a;code = 97
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = r;code = 114
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char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = g;code = 103
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char = u;code = 117
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char = a;code = 97
char = t;code = 116
char = h;code = 104
char = i;code = 105
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char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = r;code = 114
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char = p;code = 112
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char = i;code = 105
char = l;code = 108
char = i;code = 105
char = c;code = 99
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char = g;code = 103
char = r;code = 114
char = o;code = 111
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char = p;code = 112
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
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char = w;code = 119
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char = d;code = 100
char = e;code = 101
char = ;code = 32
char = v;code = 118
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
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char = h;code = 104
char = e;code = 101
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char = a;code = 97
char = p;code = 112
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
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char = e;code = 101
char = n;code = 110
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char = .;code = 46
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char = C;code = 67
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char = a;code = 97
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char = p;code = 112
char = o;code = 111
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char = o;code = 111
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char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = s;code = 115
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char = a;code = 97
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char = e;code = 101
char = ;code = 32
char = a;code = 97
char = s;code = 115
char = s;code = 115
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char = e;code = 101
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char = w;code = 119
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char = t;code = 116
char = h;code = 104
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char = c;code = 99
char = h;code = 104
char = a;code = 97
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char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
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char = e;code = 101
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
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char = v;code = 118
char = i;code = 105
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char = y;code = 121
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char = i;code = 105
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = c;code = 99
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char = ;code = 32
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char = l;code = 108
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char = r;code = 114
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char = r;code = 114
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char = s;code = 115
char = p;code = 112
char = e;code = 101
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char = i;code = 105
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char = s;code = 115
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char = h;code = 104
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char = ;code = 32
char = f;code = 102
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char = s;code = 115
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char = (;code = 40
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char = ;code = 32
char = 5;code = 53
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char = F;code = 70
char = U;code = 85
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char = x;code = 120
char = a;code = 97
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char = i;code = 105
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
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char = c;code = 99
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char = m;code = 109
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char = a;code = 97
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char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
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char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
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char = ;code = 32
char = A;code = 65
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
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char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = d;code = 100
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = o;code = 111
char = r;code = 114
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char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = M;code = 77
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = S;code = 83
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char = T;code = 84
char = 1;code = 49
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char = g;code = 103
char = e;code = 101
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char = e;code = 101
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char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = w;code = 119
char = e;code = 101
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = );code = 41
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
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char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = R;code = 82
char = R;code = 82
char = s;code = 115
char = );code = 41
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = y;code = 121
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = -;code = 45
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = k;code = 107
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = s;code = 115
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char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = -;code = 45
char = s;code = 115
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = <;code = 60
char = b;code = 98
char = r;code = 114
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char = >;code = 62
char = <;code = 60
char = b;code = 98
char = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = R;code = 82
char = E;code = 69
char = S;code = 83
char = U;code = 85
char = L;code = 76
char = T;code = 84
char = S;code = 83
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = P;code = 80
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = s;code = 115
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char = h;code = 104
char = e;code = 101
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char = e;code = 101
char = r;code = 114
char = o;code = 111
char = z;code = 122
char = y;code = 121
char = g;code = 103
char = o;code = 111
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
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char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
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char = o;code = 111
char = r;code = 114
char = p;code = 112
char = h;code = 104
char = i;code = 105
char = s;code = 115
char = m;code = 109
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char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = a;code = 97
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char = R;code = 82
char = R;code = 82
char = ;code = 32
char = =;code = 61
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char = 0;code = 48
char = .;code = 46
char = 4;code = 52
char = 7;code = 55
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char = (;code = 40
char = 9;code = 57
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char = %;code = 37
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char = c;code = 99
char = e;code = 101
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char = i;code = 105
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char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = a;code = 97
char = l;code = 108
char = ;code = 32
char = [;code = 91
char = C;code = 67
char = I;code = 73
char = ];code = 93
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 2;code = 50
char = 7;code = 55
char = ;code = 32
char = t;code = 116
char = o;code = 111
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char = 0;code = 48
char = .;code = 46
char = 8;code = 56
char = 1;code = 49
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char = ;code = 32
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char = m;code = 109
char = p;code = 112
char = a;code = 97
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char = h;code = 104
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char = a;code = 97
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char = i;code = 105
char = e;code = 101
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char = s;code = 115
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char = h;code = 104
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = z;code = 122
char = y;code = 121
char = g;code = 103
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char = s;code = 115
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char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
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char = I;code = 73
char = l;code = 108
char = e;code = 101
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
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char = e;code = 101
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char = f;code = 102
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char = ;code = 32
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char = a;code = 97
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char = o;code = 111
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char = h;code = 104
char = i;code = 105
char = s;code = 115
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char = h;code = 104
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = n;code = 110
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char = R;code = 82
char = R;code = 82
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 1;code = 49
char = 6;code = 54
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char = (;code = 40
char = 9;code = 57
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char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 4;code = 52
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char = t;code = 116
char = o;code = 111
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char = 0;code = 48
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char = 6;code = 54
char = 3;code = 51
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char = .;code = 46
char = ;code = 32
char = A;code = 65
char = f;code = 102
char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = a;code = 97
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char = u;code = 117
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char = n;code = 110
char = t;code = 116
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char = o;code = 111
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char = o;code = 111
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char = m;code = 109
char = a;code = 97
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char = c;code = 99
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char = u;code = 117
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char = s;code = 115
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char = w;code = 119
char = e;code = 101
char = r;code = 114
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char = (;code = 40
char = 9;code = 57
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char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ;code = 32
char = =;code = 61
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char = 0;code = 48
char = .;code = 46
char = 0;code = 48
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char = o;code = 111
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char = V;code = 86
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char = ;code = 32
char = a;code = 97
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char = l;code = 108
char = e;code = 101
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char = (;code = 40
char = 9;code = 57
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char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 3;code = 51
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char = 1;code = 49
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char = 1;code = 49
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char = V;code = 86
char = a;code = 97
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
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char = P;code = 80
char = ;code = 32
char = =;code = 61
char = .;code = 46
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char = .;code = 46
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char = P;code = 80
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char = i;code = 105
char = e;code = 101
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char = V;code = 86
char = a;code = 97
char = l;code = 108
char = /;code = 47
char = (;code = 40
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
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char = V;code = 86
char = a;code = 97
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char = ;code = 32
char = g;code = 103
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char = f;code = 102
char = ;code = 32
char = 2;code = 50
char = 4;code = 52
char = .;code = 46
char = 9;code = 57
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result sql = BACKGROUND : Members of the glutathione S-transferase (GST) superfamily are important in cellular defense mechanisms. These enzymes attach reduced glutathione to electrophilic groups in a wide variety of toxic compounds, including chemotherapeutic agents. Certain polymorphisms in GSTs are associated with changes in enzyme activity, sensitivity to chemotherapy, and overall patient survival. In a retrospective study, we investigated associations between common polymorphisms in genes for several GST subclasses (GSTP1, GSTT1, GSTM1) and survival of patients with metastatic colorectal cancer receiving 5-fluorouracil (5-FU)/oxaliplatin chemotherapy.

METHODS : During 1998-2000, 107 previously treated patients with advanced colorectal cancer received 5-FU/oxaliplatin combination chemotherapy. Associations between deletion polymorphisms in GSTM1 and GSTT1 genes and between a polymorphism in the GSTP1 gene that generates an Ile(105)Val in the GSTP1 protein and survival were evaluated using relative risks (RRs) of dying and the log-rank test. All statistical tests were two-sided.

RESULTS : Patients heterozygous for the GSTP1 polymorphism had an RR = 0.47 (95% confidence interval [CI] = 0.27 to 0.81) compared with patients homozygous for the GSTP1 (105)Ile allele. Patients homozygous for the mutant polymorphism had an RR = 0.16 (95% CI = 0.04 to 0.63). After adjustment for performance status and tumor site, the stratified RRs were 0.28 (95% CI = 0.07 to 1.10) for patients with two (105)Val alleles and 0.64 (95% CI = 0.36 to 1.16) for those with one (105)Val allele (P =.042). Patients with the (105)Val/(105)Val genotype survived a median of 24.9 months, those with the (105)Ile/(105)Ile genotype a median of 7.9 months, and those with the (105)Ile/(105)Val genotype a median of 13.3 months (P<.001). The GSTM1 and GSTT1 genotypes were not associated with survival or clinical response.

CONCLUSIONS : The GSTP1 Ile(105)Val polymorphism is associated in a dose-dependent fashion with increased survival of patients with advanced colorectal cancer receiving 5-FU/oxaliplatin chemotherapy.

Publication: J. Natl. Cancer Inst. 2002 Jun 19 ;94(12)::936-42.
Publication Date: 2002 Jun 19
Study Author(s): Stoehlmacher, Jan;Park, David J;Zhang, Wu;Groshen, Susan;Tsao-Wei, Denice D;Yu, Mimi C;Lenz, Heinz-Josef;
Institution: Department of Medical Oncology, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA 90033, USA.
Shortcut link to this study:
BACKGROUND : Members of the glutathione S-transferase (GST) superfamily are important in cellular defense mechanisms. These enzymes attach reduced glutathione to electrophilic groups in a wide variety of toxic compounds, including chemotherapeutic agents. Certain polymorphisms in GSTs are associated with changes in enzyme activity, sensitivity to chemotherapy, and overall patient survival. In a retrospective study, we investigated associations between common polymorphisms in genes for several GST subclasses (GSTP1, GSTT1, GSTM1) and survival of patients with metastatic colorectal cancer receiving 5-fluorouracil (5-FU)/oxaliplatin chemotherapy.

METHODS : During 1998-2000, 107 previously treated patients with advanced colorectal cancer received 5-FU/oxaliplatin combination chemotherapy. Associations between deletion polymorphisms in GSTM1 and GSTT1 genes and between a polymorphism in the GSTP1 gene that generates an Ile(105)Val in the GSTP1 protein and survival were evaluated using relative risks (RRs) of dying and the log-rank test. All statistical tests were two-sided.

RESULTS : Patients heterozygous for the GSTP1 polymorphism had an RR = 0.47 (95% confidence interval [CI] = 0.27 to 0.81) compared with patients homozygous for the GSTP1 (105)Ile allele. Patients homozygous for the mutant polymorphism had an RR = 0.16 (95% CI = 0.04 to 0.63). After adjustment for performance status and tumor site, the stratified RRs were 0.28 (95% CI = 0.07 to 1.10) for patients with two (105)Val alleles and 0.64 (95% CI = 0.36 to 1.16) for those with one (105)Val allele (P =.042). Patients with the (105)Val/(105)Val genotype survived a median of 24.9 months, those with the (105)Ile/(105)Ile genotype a median of 7.9 months, and those with the (105)Ile/(105)Val genotype a median of 13.3 months (P<.001). The GSTM1 and GSTT1 genotypes were not associated with survival or clinical response.

CONCLUSIONS : The GSTP1 Ile(105)Val polymorphism is associated in a dose-dependent fashion with increased survival of patients with advanced colorectal cancer receiving 5-FU/oxaliplatin chemotherapy.
PMID: 12072547

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