BACKGROUND: Altered DNA repair capacity due to polymorphisms in DNA repair genes may modify response to Bacillus Calmette-Guerin (BCG) immunotherapy for high risk superficial bladder cancer (SBC).We evaluated the prospective outcome of exicision repair cross complementing group 2 (ERCC2) and apurinic/apyriminidic endonuclease (APEX1) gene in tumor recurrence after BCG immunotherapy in SBC patients. MATERIALS AND METHODS: The study included 135 SBC patients, of which BCG immunotherapy was received by 74 patients. Genotyping was performed for ERCC2 Asp(312)Asn (G > A), Lys751Gln (A > C), and APEX1 Asp(148)Glu (T > G) polymorphisms by restriction fragment length polymorphism PCR and amplification refractory mutation system (ARMS) methods. RESULTS: Multiple Cox regression analysis demonstrated association of variant genotype of ERCC2 (312)AA polymorphism with high risk of recurrence in BCG treated patients (HR = 3.07, P = 0.016, P ( c ) = 0.048). Patients with the ERCC2 (312)AA polymorphic genotypes showed shorter recurrence free survival (log-rank, P = 0.005; AA/GA + AA = 14/44) who received BCG treatment. Overall, risk of recurrence in bladder cancer was observed with smokers and size of tumors (1-3 cm) (HR = 1.86, P = 0.023 and HR = 3.19, P = 0.031, respectively). Smokers were identified to be at elevated risk in BCG treated patients (HR = 2.84, P = 0.005). No association was observed with the (ERCC2 Lys(751)Gln and APEX1 Asp(148)Glu) polymorphisms and risk of recurrence. CONCLUSION: Our data suggested variant (AA) of ERCC2 312 AA genotype to be associated with high risk of tumor recurrence and reduced recurrence free survival in superficial bladder cancer patients.
BACKGROUND: Altered DNA repair capacity due to polymorphisms in DNA repair genes may modify response to Bacillus Calmette-Guerin (BCG) immunotherapy for high risk superficial bladder cancer (SBC).We evaluated the prospective outcome of exicision repair cross complementing group 2 (ERCC2) and apurinic/apyriminidic endonuclease (APEX1) gene in tumor recurrence after BCG immunotherapy in SBC patients. MATERIALS AND METHODS: The study included 135 SBC patients, of which BCG immunotherapy was received by 74 patients. Genotyping was performed for ERCC2Asp(312)Asn (G > A), Lys751Gln (A > C), and APEX1Asp(148)Glu (T > G) polymorphisms by restriction fragment length polymorphism PCR and amplification refractory mutation system (ARMS) methods. RESULTS: Multiple Cox regression analysis demonstrated association of variant genotype of ERCC2 (312)AA polymorphism with high risk of recurrence in BCG treated patients (HR = 3.07, P = 0.016, P ( c ) = 0.048). Patients with the ERCC2 (312)AA polymorphic genotypes showed shorter recurrence free survival (log-rank, P = 0.005; AA/GA + AA = 14/44) who received BCG treatment. Overall, risk of recurrence in bladder cancer was observed with smokers and size of tumors (1-3 cm) (HR = 1.86, P = 0.023 and HR = 3.19, P = 0.031, respectively). Smokers were identified to be at elevated risk in BCG treated patients (HR = 2.84, P = 0.005). No association was observed with the (ERCC2Lys(751)Gln and APEX1Asp(148)Glu) polymorphisms and risk of recurrence. CONCLUSION: Our data suggested variant (AA) of ERCC2 312 AA genotype to be associated with high risk of tumor recurrence and reduced recurrence free survival in superficial bladder cancerpatients.
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