Association of rs2294008 (PSCA) Gene polymorphism in Urothelial Bladder Cancer of South Indian Population

Document Type : Research Articles

Authors

1 Department of Urology, JN Medical College, KLE Academy of Higher Education and Research (Deemed-to-be-University), JNMC Campus, Belagavi-590010, India.

2 Urinary Biomarkers Research Centre, KLE Academy of Higher Education and Research, India.

3 Department of Biotechnology, KAHER‟s Dr. Prabhakar Kore Basic Science Research Center, III Floor, V. K. Institute of Dental Sciences Campus, Nehru Nagar, Belagavi-590010, India.

4 Department of Biochemistry, JGMM Medical College, KLE Academy of Higher Education & Research (Deemed-to-be-University), Hubballi-580032, India.

Abstract

Background: Urothelial Bladder cancer (UBC) is a significant health problem worldwide. Prostate stem cell antigen (PSCA) gene has been reported earlier in Genome Wide Association Study (GWAS) for the risk of UBC. It is highly expressed in urothelial bladder tumours and considered to be involved in the cell proliferation inhibition and/or cell-death induction activity. The study aims to investigate PSCA gene as a possible marker for the diagnosis and prognosis of urothelial bladder cancer. Patients and Methods: We genotyped PSCA rs2294008C/T gene by Real Time Taqman® probes to evaluate the risk of UBC in histologically confirmed bladder tumour patients 107 and healthy controls 105 (age and gender matched) in a hospital-based setting from South Indian population. Statistical analysis was carried out using (SPSS ver 22.0 Armonk NY, USA). Results: The heterozygous CT genotype showed increased significance risk to UBC with PSCA rs2294008 C/T having 2.77 folds risk (p<0.0001). The variant allele T was also significantly associated with UBC risk (p<0.0001; OR=3.349) for PSCA rs2294008C/T. A significant UBC risk was noted when risk was evaluated with tumor-grade-stage level for PSCA rs2294008C/T with heterozygous CT genotype for high grade tumours (p<0.001; OR=1.984). The smoking factor was significantly modulated with the risk of UBC in patients with heterozygous CT genotype (p<0.0001) for PSCA rs2294008C/T gene polymorphism. Urothelial Bladder cancer patients receiving BCG treatment showed no significant association with genotype of PSCA. Conclusions: The present study has unveiled a complex intervention of PSCA rs2294008C/T conferring a higher risk of UBC risk among smokers in South Indian population, providing evidence that it may contribute to bladder carcinogenesis regardless of ethnicity. These findings suggest that the PSCA rs2294008C/T polymorphism of PSCA gene could be served as a biomarker for genetic susceptibility to bladder cancer in Indian populations.

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