The Role of Vitamin D Receptor Polymorphisms in Predicting the Response to Therapy for Nonmuscle Invasive Bladder Carcinoma

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Abstract

Purpose:

Clinical and pathological predictors of bladder carcinoma recurrence and progression are relatively well defined. However, there is a paucity of genetic data specifically on the association of single nucleotide polymorphisms in specific genes for predicting recurrence and progression following immunotherapy. The VDR gene was found to regulate the immunomodulatory effects of vitamin D and it enhances the innate immunity system. We evaluated 3 VDR single nucleotide polymorphisms and their predictive role on the response to immunotherapy.

Materials and Methods:

Patients with bladder cancer at intermediate-high risk who underwent post-transurethral resection intravesical bacillus Calmette-Guérin in Singapore and Hong Kong from 1995 to 2014 were recruited for analysis. We evaluated 3 VDR single nucleotide polymorphisms using polymerase chain reaction. Kaplan-Meier survival curves and relationships with outcomes were analyzed by multivariable Cox regression.

Results:

A total of 338 predominantly Chinese patients were included in study. Individuals carrying the VDR genotype Bsm A/G were significantly associated with lower time to recurrence after bacillus Calmette-Guérin therapy (p <0.001). On multivariable analysis the HR of recurrence in patients with the Bsm A allele was 3.95 times that in patients without the allele (p = 0.037). Patients with the VDR GATC subhaplotype were 3.05 times more likely than patients with other subhaplotypes to experience recurrences (p = 0.003). Study limitations include the small sample size and the lack of information on previous bacillus Calmette-Guérin vaccine exposure and on vitamin D levels.

Conclusions:

Our findings in this study suggest that various VDR single nucleotide polymorphisms are associated with recurrences after bacillus Calmette-Guérin immunotherapy. Further functional studies should be performed to elucidate the significance of the VDR gene in the management of bladder cancer and the potential therapy implications.

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