IL-8 −251 T > A Polymorphism Is Associated with Bladder Cancer Susceptibility and Outcome after BCG Immunotherapy in a Northern Indian Cohort

Background and Aims

Chemokines and transcription factor NF-κB play a pivotal role in development of carcinoma of the bladder (CaB). The present study was conducted to analyze the association of chemokines IL-8 −251 T>A and +678 C>T and NF-κB −94 (ATTG) insertion/deletion polymorphisms with the risk of CaB and outcome after bacillus Calmette-Guerin (BCG) immunotherapy in a cohort of northern India.

Methods

Histologically confirmed 205 CaB cases and 270 controls were included. Of these, 71 patients were treated with BCG immunotherapy. Genotyping was done using allele-specific PCR methodology.

Results

The variant genotype (AA) of IL-8 −251 polymorphism was associated with more than 2-fold risk of CaB (OR 2.12; p = 0.003; 95% CI 1.28–3.52). None of the other genotypes showed association with CaB risk. Subsequently, the diplotype −251A/+678T demonstrated a 1.8-fold increased risk for CaB (OR 1.84, 95% CI 1.37–2.47). Furthermore, −251 AA genotypes reduced the risk of recurrence after BCG immunotherapy (AA; HR 0.12; 95% CI 0.04–0.41). Subsequently, improved recurrence-free survival (mean recurrence-free survival for GG, GA and AA genotypes was 24, 39 and 53 months respectively). Similarly, NF-κB ATTG Ins/Ins genotype was at reduced risk of recurrence after BCG treatment compared to Del/Del genotype, which exhibited a 2.5-fold increased risk of recurrence in patients treated with BCG immunotherapy (HR, 2.53; 95% CI 1.00–6.36). Subsequently, mean recurrence-free survival (Ins/Ins, 41; Ins/Del, 44 and Del/Del, 10 months; log rank, 0.030).

Conclusions

Our results suggested that the IL-8 −251T>A polymorphism may be a relevant host susceptibility factor for bladder carcinoma development and may influence outcome after BCG immunotherapy. Similarly, NF-κB ATTG polymorphism may also modify risk-free survival of BCG-treated patients.

Key Words: Carcinoma of bladder, bacillus Calmette-Guerin, Recurrence, Interleukin-8, Haplotype, NF-κB