Identifying polymorphisms that modulate response to Bacillus Calmette-Guerin therapy in patients with non-muscle invasive bladder carcinoma

You have accessJournal of UrologyBladder Cancer: Non-invasive III1 Apr 2018PD66-10 IDENTIFYING POLYMORPHISMS THAT MODULATE RESPONSE TO BACILLUS CALMETTE-GUERIN THERAPY IN PATIENTS WITH NON-MUSCLE INVASIVE BLADDER CARCINOMA Ziting Wang, Jen-Hwei Sng, Yew Koon Lim, Esuvaranathan Kesavan, Ratha Mahendran, Lata Raman Nee Mani, Yiong Huak Chan, Jeremy Yuen Chun Yeoh, Chi Fai Ng, Shu Yin Eddie Chan, and Edmund Chiong Ziting WangZiting Wang More articles by this author , Jen-Hwei SngJen-Hwei Sng More articles by this author , Yew Koon LimYew Koon Lim More articles by this author , Esuvaranathan KesavanEsuvaranathan Kesavan More articles by this author , Ratha MahendranRatha Mahendran More articles by this author , Lata Raman Nee ManiLata Raman Nee Mani More articles by this author , Yiong Huak ChanYiong Huak Chan More articles by this author , Jeremy Yuen Chun YeohJeremy Yuen Chun Yeoh More articles by this author , Chi Fai NgChi Fai Ng More articles by this author , Shu Yin Eddie ChanShu Yin Eddie Chan More articles by this author , and Edmund ChiongEdmund Chiong More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3006AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Bacillus Calmette-Guerin (BCG) immunotherapy has a considerable failure rate. Various centres have found associations between polymorphisms in genes involved in the immune inflammatory pathways and treatment outcomes. We evaluated a panel of polymorphisms in a prospectively maintained cohort of Asian non-muscle invasive bladder carcinoma (NMIBC) patients. MicroArray analysis was also performed to assess candidate variants and their association with BCG immunotherapy response. METHODS 218 NMIBC patients that had received BCG therapy and 200 normal controls from the Chinese University of Hong Kong and National University Hospital of Singapore were recruited for the study. Single Nucleotide Polymorphisms (SNP) were classified by High Resolution Melting analysis and Sequence analysis. 18 SNPs from the Natural Resistance-Associated Macrophage Protein1 (NRAMP1)gene and 8 SNPs from the immune response gene family were evaluated. Kaplan-Meier together with Log-Rank test and Cox regression methods were used to analyse the data. Illumina Infinium OncoArray-500K BeadChip MicroArray were then used to interrogate 12 BCG responders and 12 non-responders (6 recurrences and 6 progressions). RESULTS Polymorphism genotype distributions were similar between controls and patients, in accordance to the Hardy-Weinberg equilibrium. NRAMP1 rs34448891 Allele 3/3 were associated with increased incidence of cancer progression (p=0.014) compared to Allele 3/2. Patients carrying the Interleukin 17A rs2275913 G/A and G/G genotype were also found to have shorter time to recurrence (p=0.004). The Interleukin 18 receptor 1 rs3771171 A/A genotype was associated with shorter time to recurrence (p=0.04) and time to progression (p=0.043). The MicroArray Analysis revealed that rs8125878 (GA) of chromosome 20 and rs6569926 (AG) of chromosome 6 both carried prognostication value, with all responders having a homozygous genotype and all non-responders having a heterozygous genotype. CONCLUSIONS Our findings show that specific polymorphisms in NRAMP1, IL17A and IL18R1 correlate with response to BCG therapy in Asian NMIBC patients. Further functional studies should be performed to elucidate the significance of these genes in the management of bladder cancer and potential therapy implications. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1234 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Ziting Wang More articles by this author Jen-Hwei Sng More articles by this author Yew Koon Lim More articles by this author Esuvaranathan Kesavan More articles by this author Ratha Mahendran More articles by this author Lata Raman Nee Mani More articles by this author Yiong Huak Chan More articles by this author Jeremy Yuen Chun Yeoh More articles by this author Chi Fai Ng More articles by this author Shu Yin Eddie Chan More articles by this author Edmund Chiong More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...