MP83-06 VARIANTS IN THE INFLAMMATORY GENE PATHWAY ARE PREDICTIVE OF RECURRENCE AND PROGRESSION IN PATIENTS WHO RECEIVED BACILLUS OF CALMETTE AND GUÉRIN (BCG) FOR NON-MUSCLE INVASIVE BLADDER CANCER

Abstract

You have accessJournal of UrologyBladder Cancer: Basic Research & Pathophysiology IV1 Apr 2016MP83-06 VARIANTS IN THE INFLAMMATORY GENE PATHWAY ARE PREDICTIVE OF RECURRENCE AND PROGRESSION IN PATIENTS WHO RECEIVED BACILLUS OF CALMETTE AND GUÉRIN (BCG) FOR NON-MUSCLE INVASIVE BLADDER CANCER Stephen Williams, Ashish Kamat, Chinedu Mmeje, Edwin Morales, Yuanqing Ye, Maosheng Huang, David Wang, Colin Dinney, and Xifeng Wu Stephen WilliamsStephen Williams More articles by this author , Ashish KamatAshish Kamat More articles by this author , Chinedu MmejeChinedu Mmeje More articles by this author , Edwin MoralesEdwin Morales More articles by this author , Yuanqing YeYuanqing Ye More articles by this author , Maosheng HuangMaosheng Huang More articles by this author , David WangDavid Wang More articles by this author , Colin DinneyColin Dinney More articles by this author , and Xifeng WuXifeng Wu More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2016.02.2188AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Intravesical Bacillus of Calmette and Guérin (BCG) immunotherapy for non-muscle invasive bladder cancer (NMIBC) has previously been proven to decrease recurrence and progression of disease. Germline genetic variation within the inflammatory gene pathway may identify which patients are less likely to respond to BCG treatment. We wanted to assess recurrence and progression outcomes according to genetic variants in the inflammatory gene pathway among NMIBC patients treated with or without BCG immunotherapy after transurethral resection (TUR). METHODS This study included 349 patients diagnosed with NMIBC as part of an ongoing bladder cancer case-control study at MD Anderson Cancer Center since 1995. We used Cox proportional hazards regression analyses to identify single nucleotide polymorphisms (SNPs) in the inflammatory gene pathway as predictors for recurrence and progression. Cumulative effect analysis was performed and corresponding SNPs were identified both individually and jointly with increasing number of unfavorable genotypes. RESULTS We identified 20 SNPs that were significantly associated with recurrence outcomes in patients treated with BCG but not significant in the TUR only group. Of these, 16 SNPs were associated with a significant benefit following BCG treatment but increased risk of recurrence in TUR only group. The most significant association was observed for SNP rs3138056 in the gene NFKBIA which conferred a 69% (95% Confidence Interval (CI), 0.17-0.55) reduction in risk of recurrence. We identified 15 SNPs associated with a significant benefit of reduced risk of progression following BCG treatment but increased risk of progression in the TUR only group. Cumulative analysis of these high benefit loci for BCG treatment showed a significant dose response relationship. Compared to individuals with = 3 beneficial genotype, individuals carrying 6 beneficial genotype had a 71% (95% CI 0.16-0.52) reduction in the risk of recurrence in the BCG group, but a 1.42-fold (95% CI 0.77-2.63) increased risk of recurrence in TUR only group. We are currently in the process of validating these SNPs. CONCLUSIONS This study identified a set of SNPs which may be useful in identifying patients most likely to benefit from BCG treatment. These findings warrant further validation in order to improve subgroup stratification to identify patients most likely to benefit from BCG immunotherapy versus upfront radical cystectomy and future development of potential targeted therapies. © 2016FiguresReferencesRelatedDetails Volume 195Issue 4SApril 2016Page: e1083 Advertisement Copyright & Permissions© 2016MetricsAuthor Information Stephen Williams More articles by this author Ashish Kamat More articles by this author Chinedu Mmeje More articles by this author Edwin Morales More articles by this author Yuanqing Ye More articles by this author Maosheng Huang More articles by this author David Wang More articles by this author Colin Dinney More articles by this author Xifeng Wu More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...