The Role of Vitamin D Receptor Polymorphisms in Predicting the Response to Therapy for Nonmuscle Invasive Bladder Carcinoma
- Resource Type
- Authors
- Yiong Huak Chan; Henry C.C. Lim; Jeremy Yuen-Chun Teoh; Eddie Shu-Yin Chan; Ziting Wang; Ratha Mahendran; Kesavan Esuvaranathan; Nerice Ngiam; Lata Raman Nee Mani; Y.K. Lim; Chi-Fai Ng; Edmund Chiong
- Source
- Journal of Urology. 200:737-742
- Subject
- Adult
0301 basic medicine
Oncology
medicine.medical_specialty
Urology
medicine.medical_treatment
Single-nucleotide polymorphism
Polymorphism, Single Nucleotide
Calcitriol receptor
03 medical and health sciences
0302 clinical medicine
Adjuvants, Immunologic
Internal medicine
Carcinoma
medicine
Vitamin D and neurology
Humans
Neoplasm Invasiveness
Longitudinal Studies
Prospective Studies
Survival analysis
Aged
Aged, 80 and over
Bladder cancer
business.industry
Immunotherapy
Middle Aged
Prognosis
medicine.disease
030104 developmental biology
Urinary Bladder Neoplasms
030220 oncology & carcinogenesis
BCG Vaccine
Receptors, Calcitriol
business
BCG vaccine
- Language
- ISSN
- 1527-3792
0022-5347
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.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.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 (p0.001). 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.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.