Calais Da Silva, F.M., Calais Da Silva, F.E., Ligeiro, D., Sobral, J., Trindade, H.

Presented on March 21, 2007

Introduction & Objectives: Gene polymorphisms in key immunoregulatory molecules may contribute to the heterogeneity in outcome between individuals with bladder superficial carcinome receiving the immunotherapeutic treatment with BCG. This study aims to verify and identify cytokine gene polymorphisms that could influence the immune response to BCG and antitumoural action in those patients. 

Material & Methods: We studied 90 patients, after turb and BCG intravesical, there were 72 responders (80 %), 18 non-responders ( 20%) all patients are multiple or recurrent except T1 G3 or Cis, the median follow up is 4,5 years.  The cytokines single nucleotide polymorphisms (SNP’s) (IL-1a (-889T/C), IL-1b (-511C/T), IL-1b (3962T/C), IL-1R (970 C/T), IL-1Ra (11100 T/C), IL-4 (-590 C/T), IL4-Ra (+576 G/A), IL-6 (-174 G/C), IL-10 (–1082GA/-819CT/-592CA), IL-12p35 (-916C/T), TGF-b (Codon 10 C/T), TNF-a (488GA/-238GA/-308GA), TNF-b (252 G/A), IFN-g (+874 T/A)) genotypes were assessed by PCR with Sequence Specific Primers (PCR-SSP). Genotypes and allele frequencies of responders and non-responders (with tumour recidive) to the treatment were compared and evaluated by the two-sided Fisher's exact test or Chi square and odds ratios (OR) were calculated as an estimate of relative risk. 

Results: It was found a correlation of cytokine gene polymorphisms to outcome of patients for both the genotype and haplotype TNF-a 488G/-238G/-308G frequencies, which are significantly higher in patients with tumour recidive after BCG treatment (non-responders 72,2% vs responders 42% OR=3,6; 95%CI 1.15 to 11.17 p=0.033). From the other genes studied, we could depict a weak association of the IL-1R 970 T/T genotype, with a higher frequency in non-responder patients (27,8% vs 4.2% in responders, p<0.05) and with IL-10 –1082 A allele also more frequent in non-responders to BCG (75% vs 54,8%; p<0.05). 

Conclusions: These results suggest that host genetics of immune regulatory molecules may play a role in predicting the antitumoural response after BCG treatment of bladder cancer. Confirmation of these findings in other populations is required.

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