IL-8 -251 T > A polymorphism is associated with bladder cancer susceptibility and outcome after BCG immunotherapy in a northern Indian cohort.
OBJECTIVE
Chemokines and transcription factor NF-kappaB 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-kappaB -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-kappaB 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 -251 T>A polymorphism may be a relevant host susceptibility factor for bladder carcinoma development and may influence outcome after BCG immunotherapy. Similarly, NF-kappaB ATTG polymorphism may also modify risk-free survival of BCG-treated patients.
Ahirwar
Dinesh Kumar
DK
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India.
Mandhani
Anil
A
Mittal
Rama Devi
RD
D000368:Aged; D001500:BCG Vaccine / Q000627:therapeutic use*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007167:Immunotherapy; D007194:India; D016209:Interleukin-8 / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000235:genetics; D011110:Polymorphism, Genetic; D012008:Recurrence; D014026:Nicotiana; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology / Q000517:prevention & control
D001500:BCG Vaccine; D016209:Interleukin-8; D016328:NF-kappa B