Abstract
Superficial bladder tumors have a high recurrence rate and 10% to 20% of recurrences progress to invasive cancer. Recurrence and progression can best be prevented by nonspecific immunotherapy using intravesical BCG instillations. The NRAMP1 gene has been implicated in susceptibility to infectious and autoimmune diseases, and in response to BCG in murine models. We evaluated the association of 5 NRAMP1 gene polymorphisms with the risk of superficial bladder cancer recurrence and response to immunotherapy. The (GT)n, 274 C/T, 469 + 14 G/C, 1465-85 G/A and D534N polymorphisms were tested on peripheral blood DNA of individuals from three cohorts: 37 bladder tumor patients treated by transurethral resection and without recurrence after up to eight years, 67 patients at high risk of recurrence of their bladder tumors and treated with BCG and 109 controls, using restriction fragment length polymorphisms or microsatellite analysis following PCR amplification. The D543N G:A genotype was found more frequently in patients at high risk of recurrence (8 of 67 or 12%) than in controls (2 of 109 or 2%) (p = 0.007). Patients with nonrecurrent tumors showed no difference with controls (1 of 37 or 3%) (p = 1.0). Moreover, in multivariate and sur...Continue Reading
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