SIU 2017: The Role of Vitamin D Receptor Polymorphisms in Predicting Response to Therapy in Non-Muscle Invasive Bladder Carcinoma

Lisbon, Portugal ( Clinico-pathological 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 (SNP) of the Vitamin D Receptor (VDR) gene have also been found to be associated with response to treatment for mycobacterium. 

In this study, Dr. Wang’s group evaluated the predictive role of 3 VDR single SNPs in NMIBC patients by assessing BCG immunotherapy outcome. Peripheral blood DNA was prospectively obtained from 140 evaluable EORTC intermediate to high risk NMIBC patients, who underwent post-TURBT intravesical instillation of BCG or BCG with interferon alpha. Three 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 for analysis.

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 demonstrated that individuals carrying the VDR genotype rs1544.410 A/G were significantly associated with lower recurrence-free survival rates after BCG therapy (p=0.007). The VDR rs1544.410 "A" allele frequency was found to be higher in patients with bladder cancer recurrences (p=0.01). Furthermore, 100.0% of patients with the VDR genotype rs731236 C/C had carcinoma in situ of the bladder, compared to 20.5% of the patients with the genotype T/T and 12.5% of the patients with the genotype T/C (X2 (2) = 8.31, p=0,016). No association of VDR genotypes with progression-free survival was found.

Dr. Wang concluded that these findings suggest that polymorphisms in the VDR gene correlate with response to BCG therapy in NMIBC patients, and their potential role as predictive bio-markers of response to BCG immunotherapy should be further evaluated.

Presented by: Wang Z
Affiliation: National University Hospital, Singapore; The Chinese University of Hong Kong

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre.Twitter: @GoldbergHanan at the 37th Congress of Société Internationale d’Urologie - October 19-22, 2017- Lisbon, Portugal