Impact of nucleotide excision repair ERCC2 and base excision repair APEX1 genes polymorphism and its association with recurrence after adjuvant BCG immunotherapy in bladder cancer patients of North India
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 Asp312Asn (G > A), Lys751Gln (A > C), and APEX1 Asp148Glu (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 ERCC2312AA polymorphism with high risk of recurrence in BCG treated patients (HR = 3.07, P = 0.016, Pc = 0.048). Patients with the ERCC2312AA 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 Lys751Gln and APEX1 Asp148Glu) 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.
KeywordsBCG immunotherapy Bladder cancer DNA repair capacity Polymorphism Recurrence free survival
The study was supported by the grant of Department of Science and Technology, New Delhi Government of India, RG is thankful to Council of Scientific and Industrial Research, New Delhi for JRF and DA is thankful to Department of Biotechnology, Pune for SRF.
Department of Science and Technology, New Delhi Government of India.
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