94P - The role of vitamin D receptor polymorphisms in predicting response to therapy in non-muscle invasive bladder carcinoma

Date 11 September 2017
Event ESMO 2017 Congress
Session Poster display session
Topics Urothelial Cancers
Genitourinary Cancers
Translational Research
Presenter Kep Yong Loh
Citation Annals of Oncology (2017) 28 (suppl_5): v22-v42. 10.1093/annonc/mdx363
Authors K.Y. Loh1, Z. Wang2, Y.K. Lim3, R. Mahendran2, E. Kesavan2, E. Chiong2
  • 1Surgery, Duke-NUS Medical School, 169857 - Singapore/SG
  • 2Urology, National University Hospital, 119228 - Singapore/SG
  • 3Urology, National University Hospital, Singapore/SG

Abstract

Background

Clinicopathological factors predicting for response to Bacillus-Calmette Guerin (BCG) treatment for non-muscle invasive bladder carcinoma (NMIBC) are well defined but there is a paucity of data on genetic factors. Vitamin D has been found to have immunomodulatory effects in pre-clinical bladder cancer studies. Various single nucleotide polymorphisms of the Vitamin D Receptor (VDR) gene has also been found to be associated with response to treatment for mycobacterium. In this study, we evaluated the predictive role of 3 VDR single nucleotide polymorphisms (SNP) in patients with NMIBC in assessing BCG immunotherapy outcome.

Methods

Peripheral blood DNA was prospectively obtained from 140 evaluable EORTC intermediate to high risk NMIBC patients, who underwent post-transurethral resection intravesical regimes of BCG or BCG with interferon alpha. 3 VDR SNPs commonly implicated in susceptibility to tuberculosis infections were evaluated using high resolution melt (HRM) analysis followed by DNA sequencing. Kaplan-Meier together with Log-Rank test and Cox regression methods were used to analyze the data.

Results

Genotype frequencies were similar between the NMIBC patients and controls in accordance to the Hardy Weinberg equilibrium. Mean follow-up time was 91.9 months. Overall mean time to recurrence and progression was 25.8 months and 47.0 months respectively. Kaplan-Meier analysis indicate that individuals carrying the VDR genotype rs1544410 A/G were significantly associated with lower recurrence-free survival rates after BCG therapy (p = 0.007). The VDR rs1544410 “A” allele frequency was found to be higher in patients with bladder cancer recurrences (p = 0.01). No association of VDR genotypes with progression-free survival was found.

Conclusions

Our findings suggest that polymorphisms in the VDR gene correlate with response to BCG therapy in NMIBC patients and further work should be performed to evaluate their utility as predictive markers of response to BCG immunotherapy.

Clinical trial identification

Legal entity responsible for the study

National Healthcare group Domain Specific Review Board

Funding

None

Disclosure

All authors have declared no conflicts of interest.