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char = -;code = 45
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char = f;code = 102
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char = s;code = 115
char = e;code = 101
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char = P;code = 80
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char = r;code = 114
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char = s;code = 115
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char = s;code = 115
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char = a;code = 97
char = l;code = 108
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char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = y;code = 121
char = .;code = 46
result sql = Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-s-transferase-P1 and -M1, a retrospective cross sectional study.
Association between long-term neuro-toxicities in testicular cancer survivors and polymorphisms in glutathione-s-transferase-P1 and -M1, a retrospective cross sectional study.
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char = -;code = 45
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
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 = i;code = 105
char = e;code = 101
char = s;code = 115
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 = e;code = 101
char = d;code = 100
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = j;code = 106
char = u;code = 117
char = s;code = 115
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
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 = A;code = 65
char = l;code = 108
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = x;code = 120
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 = 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 = i;code = 105
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 = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
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 = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = u;code = 117
char = m;code = 109
char = u;code = 117
char = l;code = 108
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 = o;code = 111
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = /;code = 47
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = o;code = 111
char = m;code = 109
char = y;code = 121
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = C;code = 67
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 = t;code = 116
char = o;code = 111
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 = e;code = 101
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
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 = 45
char = A;code = 65
char = G;code = 71
char = ;code = 32
char = o;code = 111
char = r;code = 114
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 = 45
char = A;code = 65
char = A;code = 65
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = 3;code = 51
char = 7;code = 55
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 = t;code = 116
char = h;code = 104
char = e;code = 101
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 = ;code = 32
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = P;code = 80
char = 1;code = 49
char = -;code = 45
char = G;code = 71
char = G;code = 71
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = i;code = 105
char = g;code = 103
char = n;code = 110
char = i;code = 105
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 3;code = 51
char = 9;code = 57
char = ,;code = 44
char = ;code = 32
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 4;code = 52
char = 6;code = 54
char = ;code = 32
char = [;code = 91
char = 0;code = 48
char = .;code = 46
char = 2;code = 50
char = 2;code = 50
char = -;code = 45
char = 0;code = 48
char = .;code = 46
char = 9;code = 57
char = 6;code = 54
char = ];code = 93
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 2;code = 50
char = 3;code = 51
char = ,;code = 44
char = ;code = 32
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 4;code = 52
char = 2;code = 50
char = ;code = 32
char = [;code = 91
char = 0;code = 48
char = .;code = 46
char = 2;code = 50
char = 0;code = 48
char = -;code = 45
char = 0;code = 48
char = .;code = 46
char = 8;code = 56
char = 8;code = 56
char = ];code = 93
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = n;code = 110
char = i;code = 105
char = t;code = 116
char = u;code = 117
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 0;code = 48
char = 8;code = 56
char = ,;code = 44
char = ;code = 32
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 3;code = 51
char = 3;code = 51
char = ;code = 32
char = [;code = 91
char = 0;code = 48
char = .;code = 46
char = 1;code = 49
char = 4;code = 52
char = -;code = 45
char = 0;code = 48
char = .;code = 46
char = 7;code = 55
char = 4;code = 52
char = ];code = 93
char = );code = 41
char = .;code = 46
char = ;code = 32
char = F;code = 70
char = u;code = 117
char = r;code = 114
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = b;code = 98
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 = 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 = 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 = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
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 = 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
char = ;code = 32
char = (;code = 40
char = p;code = 112
char = ;code = 32
char = =;code = 61
char = ;code = 32
char = 0;code = 48
char = .;code = 46
char = 0;code = 48
char = 2;code = 50
char = 5;code = 53
char = ,;code = 44
char = ;code = 32
char = O;code = 79
char = R;code = 82
char = ;code = 32
char = 1;code = 49
char = .;code = 46
char = 8;code = 56
char = 1;code = 49
char = ;code = 32
char = [;code = 91
char = 1;code = 49
char = .;code = 46
char = 0;code = 48
char = 8;code = 56
char = -;code = 45
char = 3;code = 51
char = .;code = 46
char = 0;code = 48
char = 3;code = 51
char = ];code = 93
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 = I;code = 73
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 = l;code = 108
char = o;code = 111
char = n;code = 110
char = g;code = 103
char = -;code = 45
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = l;code = 108
char = f;code = 102
char = -;code = 45
char = r;code = 114
char = e;code = 101
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
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 = i;code = 105
char = n;code = 110
char = d;code = 100
char = u;code = 117
char = c;code = 99
char = e;code = 101
char = d;code = 100
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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
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char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
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char = e;code = 101
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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 = 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 = 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 = 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 = 46
char = ;code = 32
char = H;code = 72
char = y;code = 121
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = b;code = 98
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 = G;code = 71
char = S;code = 83
char = T;code = 84
char = -;code = 45
char = M;code = 77
char = 1;code = 49
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = a;code = 97
char = v;code = 118
char = e;code = 101
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 = 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 = a;code = 97
char = s;code = 115
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = b;code = 98
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
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
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = -;code = 45
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = G;code = 71
char = S;code = 83
char = T;code = 84
char = -;code = 45
char = P;code = 80
char = 1;code = 49
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = l;code = 108
char = s;code = 115
char = o;code = 111
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
char = a;code = 97
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 = i;code = 105
char = n;code = 110
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = r;code = 114
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result sql = BACKGROUND : To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer survivors (TCSs).

METHODS : A total of 238 TCSs, who had received cisplatin-based chemotherapy at median twelve years earlier, had participated in a long-term follow-up survey which assessed the prevalence of self-reported paresthesias in fingers/toes, Raynaud-like phenomena in fingers/toes, tinnitus, and hearing impairment. From all TCSs lymphocyte-derived DNA was analyzed for the functional A-->G polymorphism at bp 304 in GSTP1, and deletions in GST-M1 and GST-T1. Evaluation of associations between GST polymorphisms and self-reported toxicities included adjustment for prior treatment.

RESULTS : All six evaluated toxicities were significantly associated with the cumulative dose of cisplatin and/or bleomycin. Compared to TCSs with either GSTP1-AG or GSTP1-AA, the 37 TCSs with the genotype GSTP1-GG, were significantly less bothered by paresthesias in fingers and toes (p = 0.039, OR 0.46 [0.22-0.96] and p = 0.023, OR 0.42 [0.20-0.88], respectively), and tinnitus (p = 0.008, OR 0.33 [0.14-0.74]). Furthermore, absence of functional GSTM1 protected against hearing impairment (p = 0.025, OR 1.81 [1.08-3.03]).

CONCLUSION : In TCSs long-term self-reported chemotherapy-induced toxicities are associated with functional polymorphisms in GSTP1 and GSTM1. Hypothetically, absence of GST-M1 leaves more glutathione as substrate for the co-expressed GST-P1. Also intracellular inactivation of pro-apoptotic mediators represents a possible explanation of our findings. Genotyping of these GSTs might be a welcomed step towards a more individualized treatment of patients with metastatic testicular cancer.

Publication: J Transl Med 2007 ;5:70.
Publication Date: 2007
Study Author(s): Oldenburg, Jan;Kraggerud, Sigrid M;Brydøy, Marianne;Cvancarova, Milada;Lothe, Ragnhild A;Fossa, Sophie D;
Institution: Department of Clinical Cancer Research, The Norwegian Radiumhospital, Oslo, Norway. [email protected]
Shortcut link to this study:
BACKGROUND : To assess the impact of polymorphisms in Glutathione S-transferase (GST) -P1, -M1, and -T1 on self-reported chemotherapy-induced long-term toxicities in testicular cancer survivors (TCSs).

METHODS : A total of 238 TCSs, who had received cisplatin-based chemotherapy at median twelve years earlier, had participated in a long-term follow-up survey which assessed the prevalence of self-reported paresthesias in fingers/toes, Raynaud-like phenomena in fingers/toes, tinnitus, and hearing impairment. From all TCSs lymphocyte-derived DNA was analyzed for the functional A-->G polymorphism at bp 304 in GSTP1, and deletions in GST-M1 and GST-T1. Evaluation of associations between GST polymorphisms and self-reported toxicities included adjustment for prior treatment.

RESULTS : All six evaluated toxicities were significantly associated with the cumulative dose of cisplatin and/or bleomycin. Compared to TCSs with either GSTP1-AG or GSTP1-AA, the 37 TCSs with the genotype GSTP1-GG, were significantly less bothered by paresthesias in fingers and toes (p = 0.039, OR 0.46 [0.22-0.96] and p = 0.023, OR 0.42 [0.20-0.88], respectively), and tinnitus (p = 0.008, OR 0.33 [0.14-0.74]). Furthermore, absence of functional GSTM1 protected against hearing impairment (p = 0.025, OR 1.81 [1.08-3.03]).

CONCLUSION : In TCSs long-term self-reported chemotherapy-induced toxicities are associated with functional polymorphisms in GSTP1 and GSTM1. Hypothetically, absence of GST-M1 leaves more glutathione as substrate for the co-expressed GST-P1. Also intracellular inactivation of pro-apoptotic mediators represents a possible explanation of our findings. Genotyping of these GSTs might be a welcomed step towards a more individualized treatment of patients with metastatic testicular cancer.
PMID: 18162130

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