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

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Lima, L (Author) Other; Oliveira, D (Author) Other; Ferreira, JA (Author) Other; Tavares, A (Author) Other; Cruz, R (Author) Other; Rui Medeiros (Author) ICBAS; Santos, L (Author) Other

Journal

Title: BJU International

Vol. 116

Pages: 753-763

ISSN: 1464-4096

Publisher: Wiley-Blackwell

Indexing

ISI Web of Knowledge - 37 Citations

Scopus - 41 Citations

Other information

Authenticus ID: P-00G-QJJ

DOI: 10.1111/bju.12844

Abstract (EN): Objective To evaluate the predictive value of genetic polymorphisms in the context of bacille Calmette-Guerin (BCG) immunotherapy outcome and create a predictive profile that may allow discrimination of the risk of recurrence. Patients and Methods In a dataset of 204 patients treated with BCG, we evaluated 42 genetic polymorphisms in 38 genes involved in the BCG mechanism of action, using Sequenom MassARRAY (R) technology. Stepwise multivariate Cox regression was used for data mining. Results In agreement with previous studies we found that gender, age, tumour multiplicity and treatment scheme were associated with BCG failure. Using stepwise multivariate Cox regression analysis we propose the first predictive profile of BCG immunotherapy outcome and a risk score based on polymorphisms in immune system molecules [single nucleotide polymorphisms in tumour necrosis factor a (TNFA)-1031T/C (rs1799964), interleukin 2 receptor a (IL2RA) rs2104286 T/C, IL17A-197G/A (rs2275913), IL17RA-809A/G (rs4819554), IL18R1 rs3771171 T/C, intercellular adhesion molecule 1 (ICAM-1) K469E (rs5498), Fas ligand (FASL)-844T/C (rs763110) and TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1)-397T/G (rs79037040)] in association with clinicopathological variables. This risk score allows the categorisation of patients into risk groups: patients within the low-risk group have a 90% chance of successful treatment, whereas patients in the high-risk group present a 75% chance of recurrence after BCG treatment. Conclusion We have established the first predictive score of BCG immunotherapy outcome combining clinicopathological characteristics and a panel of genetic polymorphisms. Further studies using an independent cohort are warranted. Moreover, the inclusion of other biomarkers may help to improve the proposed model.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 11