IL-4 and TNF-α Polymorphisms Are Associated with Risk of Multiple Superficial Tumors or Carcinoma in situ Development

Abstract

Introduction: This study evaluates the influence of clinicopathological characteristics, bacillus Calmette-Guérin (BCG) therapeutic schedule [maintenance (mBCG) or induction (iBCG)], and TNF-α and IL-4 polymorphisms on the outcome of non-muscle-invasive bladder cancer patients treated with BCG. Material and Methods: DNA was extracted from 125 bladder cancer patients treated with BCG; TNF-308G/A and IL4-590C/T polymorphisms were genotyped. Results: The TNF-308A allele carriers had an increased risk of developing multiple tumors (OR: 2.80, p = 0.031). However, IL4-590 T carriers also had an increased risk of developing multiple and carcinoma in situ tumors (OR: 2.52, p = 0.033). For these polymorphisms, no association was found with BCG treatment outcome. When treated with iBCG, patients with multiple tumors had shorter recurrence-free survival (RFS) compared with those with a single tumor (p = 0.004); nevertheless, patients with multifocal tumors have improved RFS when treated with mBCG. Conclusions: Overall, the results suggest that multiple tumors and/or carcinoma in situ development are associated with the IL4-590C/T and TNF-308G/A polymorphisms, and emphasize the effectiveness of the mBCG schedule.

The role of functional polymorphisms in immune response genes as biomarkers of bacille Calmette-Guérin (BCG) immunotherapy outcome in bladder cancer: establishment of a predictive profile in a Southern Europe population

“…We also observed that male patients presented an increased risk of recurrence after treatment. Our present findings reinforce previous associations of these clinical variables with BCG immunotherapy response and highlight the need to include them in predictive models for this therapy.…”

“…We also observed that male patients presented an increased risk of recurrence after treatment. Our present findings reinforce previous associations of these clinical variables with BCG immunotherapy response [18,[22][23][24][25] and highlight the need to include them in predictive models for this therapy. Genetic polymorphisms in molecules involved in the BCG mechanism of action have also been recognised as good candidates to predict treatment outcome.…”

“…Our previous reports using a smaller dataset have shown that age, tumour multiplicity and the treatment scheme are associated with treatment failure . In the present study, with a larger sample, we confirmed that patients either aged >65 years, or with multiple tumours, or treated only with an induction scheme were at risk of treatment failure.…”

Systematic Review: Genetic Associations for Prognostic Factors of Urinary Bladder Cancer

“…For this review, 373 full-text articles were evaluated in depth, resulting in a final set of 112 articles for further summary (Figure 1). In total, 316 associations were extracted across all investigated outcomes as follows: age (N = 12 11-22 ), stage (N = 79 11,13,18,20,23-66 ), tumor size (N = 2 67,68 ), grade (N = 49 11,18,27,29,32,33,35…”

“…Broadly, we have differentiated between stages corresponding to NMIBC and MIBC cases. For studies reporting on NMIBC, the following endpoints were used: tumors of Tis, 61,65 T1, 37 Ta + T1, 13,18,36,39,54,58,[62][63][64]66 and Ta + T1 + Tis 32,59,60 (Supplementary Table 4). As for MIBC, most studies have defined the primary outcome as T2+ staged tum ors.…”