|
|
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result sql = Cisplatin-induced long-term hearing impairment is associated with specific glutathione s-transferase genotypes in testicular cancer survivors.
Cisplatin-induced long-term hearing impairment is associated with specific glutathione s-transferase genotypes in testicular cancer survivors.char = <;code = 60
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char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = i;code = 105
char = n;code = 110
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char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = t;code = 116
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = l;code = 108
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
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
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 = 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 = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = T;code = 84
char = C;code = 67
char = S;code = 83
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 = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = -;code = 45
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 = o;code = 111
char = d;code = 100
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = ;code = 32
char = [;code = 91
char = O;code = 79
char = R;code = 82
char = ];code = 93
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 4;code = 52
char = .;code = 46
char = 2;code = 50
char = 1;code = 49
char = ;;code = 59
char = ;code = 32
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 9;code = 57
char = 9;code = 57
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 8;code = 56
char = .;code = 46
char = 8;code = 56
char = 8;code = 56
char = ;;code = 59
char = ;code = 32
char = P;code = 80
char = ;code = 32
char = <;code = 60
char = ;code = 32
char = .;code = 46
char = 0;code = 48
char = 0;code = 48
char = 1;code = 49
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = [;code = 91
char = O;code = 79
char = L;code = 76
char = R;code = 82
char = ];code = 93
char = );code = 41
char = .;code = 46
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 = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
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 = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = T;code = 84
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ,;code = 44
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 = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
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char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
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char = r;code = 114
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 2;code = 50
char = .;code = 46
char = 7;code = 55
char = 6;code = 54
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char = ;code = 32
char = 9;code = 57
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char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
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char = 1;code = 49
char = .;code = 46
char = 3;code = 51
char = 5;code = 53
char = ;code = 32
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char = P;code = 80
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char = 0;code = 48
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char = O;code = 79
char = L;code = 76
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char = .;code = 46
char = ;code = 32
char = T;code = 84
char = C;code = 67
char = S;code = 83
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
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char = a;code = 97
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char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = 2;code = 50
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char = (;code = 40
char = G;code = 71
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char = T;code = 84
char = 1;code = 49
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char = p;code = 112
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char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = G;code = 71
char = S;code = 83
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char = M;code = 77
char = 1;code = 49
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char = p;code = 112
char = o;code = 111
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char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = 1;code = 49
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char = 5;code = 53
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = /;code = 47
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char = 0;code = 48
char = 5;code = 53
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char = a;code = 97
char = l;code = 108
char = -;code = 45
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 = ;code = 32
char = h;code = 104
char = a;code = 97
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char = b;code = 98
char = e;code = 101
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char = t;code = 116
char = e;code = 101
char = r;code = 114
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char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = T;code = 84
char = C;code = 67
char = S;code = 83
char = s;code = 115
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char = w;code = 119
char = i;code = 105
char = t;code = 116
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char = u;code = 117
char = t;code = 116
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char = t;code = 116
char = h;code = 104
char = i;code = 105
char = s;code = 115
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char = p;code = 112
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = (;code = 40
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 5;code = 53
char = .;code = 46
char = 3;code = 51
char = 5;code = 53
char = ;;code = 59
char = ;code = 32
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ,;code = 44
char = ;code = 32
char = 2;code = 50
char = .;code = 46
char = 2;code = 50
char = 5;code = 53
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 1;code = 49
char = 2;code = 50
char = .;code = 46
char = 7;code = 55
char = 6;code = 54
char = ;;code = 59
char = ;code = 32
char = P;code = 80
char = ;code = 32
char = <;code = 60
char = ;code = 32
char = .;code = 46
char = 0;code = 48
char = 0;code = 48
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = O;code = 79
char = L;code = 76
char = R;code = 82
char = );code = 41
char = .;code = 46
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 = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
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char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
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char = e;code = 101
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char = l;code = 108
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char = t;code = 116
char = ;code = 32
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char = i;code = 105
char = s;code = 115
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 = i;code = 105
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char = c;code = 99
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = o;code = 111
char = x;code = 120
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = n;code = 110
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char = d;code = 100
char = .;code = 46
result sql = PURPOSE : Cisplatin, a cornerstone of combination chemotherapy in the treatment of testicular cancer, induces hearing impairment with considerable interindividual variations. These differences might be a result of functional polymorphisms in cisplatin-detoxifying enzymes like glutathione S-transferases (GSTs).
PATIENTS AND METHODS : We identified 173 cisplatin-treated testicular cancer survivors (TCSs) who had participated in a long-term survey that included audiometric testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were categorized into leveled scales by normative decibel percentiles. Known functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105 A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction, followed by restriction enzyme cutting, and separated by gel electrophoresis.
RESULTS : The risk of having an inferior audiometric result was more than four times higher in TCSs with 105Ile/105Ile-GSTP1 or 105Val/105Ile-GSTP1 compared with 105Val/105Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P < .001 when modeled by ordinal logistic regression [OLR]). GSTM1 positivity was detrimental for hearing ability. Two combined genotypes were associated with hearing ability. The presence of pattern 1 (GSTT1 positive, GSTM1 positive, and 105Ile/105Ile-GSTP1) was associated with hearing impairment (OR = 2.76; 95% CI, 1.35 to 5.64; P = .005, OLR). TCSs with pattern 2 (GSTT1 positive, GSTM1 positive, and 105Val/105Val-GSTP1) had better hearing ability than TCSs without this pattern (OR = 5.35; 95% CI, 2.25 to 12.76; P < .001, OLR).
CONCLUSION : The presence of both alleles of 105Val-GSTP1 offered protection against cisplatin-induced hearing impairment. Two genotype patterns with good and poor protection against cisplatin-induced ototoxicity were identified.
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char = i;code = 105
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char = -;code = 45
char = i;code = 105
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char = d;code = 100
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char = l;code = 108
char = o;code = 111
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char = m;code = 109
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char = o;code = 111
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char = y;code = 121
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char = n;code = 110
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
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char = u;code = 117
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char = ;code = 32
char = c;code = 99
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char = i;code = 105
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char = o;code = 111
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char = .;code = 46
result sql = Cisplatin-induced long-term hearing impairment is associated with specific glutathione s-transferase genotypes in testicular cancer survivors.
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char = ;code = 32
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = 4;code = 52
char = ,;code = 44
char = 0;code = 48
char = 0;code = 48
char = 0;code = 48
char = ;code = 32
char = H;code = 72
char = z;code = 122
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = g;code = 103
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = c;code = 99
char = i;code = 105
char = b;code = 98
char = e;code = 101
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = c;code = 99
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = K;code = 75
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = u;code = 117
char = n;code = 110
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = a;code = 97
char = l;code = 108
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 = s;code = 115
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = g;code = 103
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = );code = 41
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 = T;code = 84
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
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 = c;code = 99
char = o;code = 111
char = d;code = 100
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = ;code = 32
char = A;code = 65
char = /;code = 47
char = G;code = 71
char = ;code = 32
char = (;code = 40
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = /;code = 47
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = );code = 41
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 = P;code = 80
char = 1;code = 49
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = y;code = 121
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = x;code = 120
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = l;code = 108
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ,;code = 44
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = l;code = 108
char = l;code = 108
char = o;code = 111
char = w;code = 119
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = z;code = 122
char = y;code = 121
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = t;code = 116
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = l;code = 108
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
char = o;code = 111
char = p;code = 112
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = .;code = 46
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 = 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 = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = r;code = 114
char = i;code = 105
char = s;code = 115
char = k;code = 107
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = a;code = 97
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = u;code = 117
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = i;code = 105
char = g;code = 103
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = T;code = 84
char = C;code = 67
char = S;code = 83
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 = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = V;code = 86
char = a;code = 97
char = l;code = 108
char = -;code = 45
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 = o;code = 111
char = d;code = 100
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = ;code = 32
char = [;code = 91
char = O;code = 79
char = R;code = 82
char = ];code = 93
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 4;code = 52
char = .;code = 46
char = 2;code = 50
char = 1;code = 49
char = ;;code = 59
char = ;code = 32
char = 9;code = 57
char = 5;code = 53
char = %;code = 37
char = ;code = 32
char = C;code = 67
char = I;code = 73
char = ,;code = 44
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 9;code = 57
char = 9;code = 57
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 8;code = 56
char = .;code = 46
char = 8;code = 56
char = 8;code = 56
char = ;;code = 59
char = ;code = 32
char = P;code = 80
char = ;code = 32
char = <;code = 60
char = ;code = 32
char = .;code = 46
char = 0;code = 48
char = 0;code = 48
char = 1;code = 49
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = g;code = 103
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = [;code = 91
char = O;code = 79
char = L;code = 76
char = R;code = 82
char = ];code = 93
char = );code = 41
char = .;code = 46
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 = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = e;code = 101
char = n;code = 110
char = o;code = 111
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = a;code = 97
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
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 = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = 1;code = 49
char = ;code = 32
char = (;code = 40
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = T;code = 84
char = 1;code = 49
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ,;code = 44
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 = p;code = 112
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = /;code = 47
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
char = I;code = 73
char = l;code = 108
char = e;code = 101
char = -;code = 45
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = );code = 41
char = ;code = 32
char = w;code = 119
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = h;code = 104
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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char = u;code = 117
char = t;code = 116
char = ;code = 32
char = t;code = 116
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
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char = R;code = 82
char = ;code = 32
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char = ;code = 32
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char = ;code = 32
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char = 5;code = 53
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char = ;code = 32
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char = I;code = 73
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char = ;code = 32
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char = 2;code = 50
char = 5;code = 53
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 1;code = 49
char = 2;code = 50
char = .;code = 46
char = 7;code = 55
char = 6;code = 54
char = ;;code = 59
char = ;code = 32
char = P;code = 80
char = ;code = 32
char = <;code = 60
char = ;code = 32
char = .;code = 46
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char = 0;code = 48
char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = O;code = 79
char = L;code = 76
char = R;code = 82
char = );code = 41
char = .;code = 46
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 = r;code = 114
char = /;code = 47
char = >;code = 62
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = C;code = 67
char = O;code = 79
char = N;code = 78
char = C;code = 67
char = L;code = 76
char = U;code = 85
char = S;code = 83
char = I;code = 73
char = O;code = 79
char = N;code = 78
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = o;code = 111
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char = h;code = 104
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char = a;code = 97
char = l;code = 108
char = l;code = 108
char = e;code = 101
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = 0;code = 48
char = 5;code = 53
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char = a;code = 97
char = l;code = 108
char = -;code = 45
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = ;code = 32
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char = f;code = 102
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char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = ;code = 32
char = p;code = 112
char = r;code = 114
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char = c;code = 99
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = g;code = 103
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = t;code = 116
char = ;code = 32
char = c;code = 99
char = i;code = 105
char = s;code = 115
char = p;code = 112
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char = n;code = 110
char = -;code = 45
char = i;code = 105
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char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
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char = o;code = 111
char = t;code = 116
char = o;code = 111
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char = c;code = 99
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = ;code = 32
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char = d;code = 100
char = e;code = 101
char = n;code = 110
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result sql = PURPOSE : Cisplatin, a cornerstone of combination chemotherapy in the treatment of testicular cancer, induces hearing impairment with considerable interindividual variations. These differences might be a result of functional polymorphisms in cisplatin-detoxifying enzymes like glutathione S-transferases (GSTs).
PATIENTS AND METHODS : We identified 173 cisplatin-treated testicular cancer survivors (TCSs) who had participated in a long-term survey that included audiometric testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were categorized into leveled scales by normative decibel percentiles. Known functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105 A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction, followed by restriction enzyme cutting, and separated by gel electrophoresis.
RESULTS : The risk of having an inferior audiometric result was more than four times higher in TCSs with 105Ile/105Ile-GSTP1 or 105Val/105Ile-GSTP1 compared with 105Val/105Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P < .001 when modeled by ordinal logistic regression [OLR]). GSTM1 positivity was detrimental for hearing ability. Two combined genotypes were associated with hearing ability. The presence of pattern 1 (GSTT1 positive, GSTM1 positive, and 105Ile/105Ile-GSTP1) was associated with hearing impairment (OR = 2.76; 95% CI, 1.35 to 5.64; P = .005, OLR). TCSs with pattern 2 (GSTT1 positive, GSTM1 positive, and 105Val/105Val-GSTP1) had better hearing ability than TCSs without this pattern (OR = 5.35; 95% CI, 2.25 to 12.76; P < .001, OLR).
CONCLUSION : The presence of both alleles of 105Val-GSTP1 offered protection against cisplatin-induced hearing impairment. Two genotype patterns with good and poor protection against cisplatin-induced ototoxicity were identified.
Publication: J. Clin. Oncol. 2007 Feb 20 ;25(6)::708-14.
Publication Date: 2007 Feb 20
Study Author(s): Oldenburg, Jan;Kraggerud, Sigrid M;Cvancarova, Milada;Lothe, Ragnhild A;Fossa, Sophie D;
Institution: Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, Oslo, Norway. [email protected]
Shortcut link to this study:
Publication Date: 2007 Feb 20
Study Author(s): Oldenburg, Jan;Kraggerud, Sigrid M;Cvancarova, Milada;Lothe, Ragnhild A;Fossa, Sophie D;
Institution: Department of Clinical Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, Oslo, Norway. [email protected]
Shortcut link to this study:
PURPOSE : Cisplatin, a cornerstone of combination chemotherapy in the treatment of testicular cancer, induces hearing impairment with considerable interindividual variations. These differences might be a result of functional polymorphisms in cisplatin-detoxifying enzymes like glutathione S-transferases (GSTs).
PATIENTS AND METHODS : We identified 173 cisplatin-treated testicular cancer survivors (TCSs) who had participated in a long-term survey that included audiometric testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were categorized into leveled scales by normative decibel percentiles. Known functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105 A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction, followed by restriction enzyme cutting, and separated by gel electrophoresis.
RESULTS : The risk of having an inferior audiometric result was more than four times higher in TCSs with 105Ile/105Ile-GSTP1 or 105Val/105Ile-GSTP1 compared with 105Val/105Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P < .001 when modeled by ordinal logistic regression [OLR]). GSTM1 positivity was detrimental for hearing ability. Two combined genotypes were associated with hearing ability. The presence of pattern 1 (GSTT1 positive, GSTM1 positive, and 105Ile/105Ile-GSTP1) was associated with hearing impairment (OR = 2.76; 95% CI, 1.35 to 5.64; P = .005, OLR). TCSs with pattern 2 (GSTT1 positive, GSTM1 positive, and 105Val/105Val-GSTP1) had better hearing ability than TCSs without this pattern (OR = 5.35; 95% CI, 2.25 to 12.76; P < .001, OLR).
CONCLUSION : The presence of both alleles of 105Val-GSTP1 offered protection against cisplatin-induced hearing impairment. Two genotype patterns with good and poor protection against cisplatin-induced ototoxicity were identified.
PATIENTS AND METHODS : We identified 173 cisplatin-treated testicular cancer survivors (TCSs) who had participated in a long-term survey that included audiometric testing and lymphocyte sampling. The hearing decibel thresholds at 4,000 Hz were categorized into leveled scales by normative decibel percentiles. Known functional polymorphisms (positive or negative) in GSTT1 and GSTM1 and codon 105 A/G (Ile/Val) in GSTP1 were analyzed by multiplex polymerase chain reaction, followed by restriction enzyme cutting, and separated by gel electrophoresis.
RESULTS : The risk of having an inferior audiometric result was more than four times higher in TCSs with 105Ile/105Ile-GSTP1 or 105Val/105Ile-GSTP1 compared with 105Val/105Val-GSTP1 (odds ratio [OR] = 4.21; 95% CI, 1.99 to 8.88; P < .001 when modeled by ordinal logistic regression [OLR]). GSTM1 positivity was detrimental for hearing ability. Two combined genotypes were associated with hearing ability. The presence of pattern 1 (GSTT1 positive, GSTM1 positive, and 105Ile/105Ile-GSTP1) was associated with hearing impairment (OR = 2.76; 95% CI, 1.35 to 5.64; P = .005, OLR). TCSs with pattern 2 (GSTT1 positive, GSTM1 positive, and 105Val/105Val-GSTP1) had better hearing ability than TCSs without this pattern (OR = 5.35; 95% CI, 2.25 to 12.76; P < .001, OLR).
CONCLUSION : The presence of both alleles of 105Val-GSTP1 offered protection against cisplatin-induced hearing impairment. Two genotype patterns with good and poor protection against cisplatin-induced ototoxicity were identified.
PMID: 17228018
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