Cluster of Differentiation 44(CD44) Gene Variants: A Putative Cancer Stem Cell Marker in Risk Prediction of Bladder Cancer in North Indian Population.
CD44 is involved in cancer-cell growth, invasion, proliferation and metastasis and is also a causal factor for acquisition of resistance to apoptosis. Therefore we evaluated different SNPs ofCD44gene viz.CD44rs187116 A/G,CD44rs4755392 A/T,CD44rs187115 C/T,CD44rs13347 C/TandCD44 rs353639 G/Tfor bladder cancer risk in North Indian population. 240 bladder cancer patients and 270 cancer free controls were recruited in this study. Genotyping was done by PCR-RFLP forCD44rs187116 A/G. However,CD44rs4755392 A/T,CD44rs187115 C/T,CD44rs13347 C/TandCD44 rs353639 G/Twere genotyped by allelic discrimination Taqman®assay. Statistical analysis was done by SPSS. In-silico analysis was done using F-SNP. We found reduced risk in variant genotype, TT of rs4755392 (p= 0.011) as well as in variant allele, T (p= 0.045). No risk was seen in rs13347, heterozygous genotype, CT (p= 0.023) and variant allele, T (p= 0.007). The dominant model, CT + TT also revealed reduced risk (p= 0.009). A marginal risk was seen in dominant model, GT + TT of rs353639 (p= 0.044) and reduced risk in variant allele T (p= 0.040). A significant manifold risk was seen in smokers carrying variant genotype, TT ofCD44rs353639 G/T(p= 0.038, OR 1.960). Haplotypic analysis revealed significant association in 4 sets viz. TCCGGp= 0.005, TTCGAp= 0.039, ACTGGp= 0.008 and TCTGAp= 0.006. In-silico analysis using F-SNP, showed altered transcriptional regulation for rs187115, rs13347 and rs353639. Our study suggests that rs353639 shows a marginal risk for bladder cancer susceptibility, whereas rs4755392 and rs13347 have reduced risk of bladder cancer and rs187115 and rs187116 had no effect on bladder cancer susceptibility in North Indians.
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014 India.
Archana
A
Verma
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014 India.
Rakesh
R
Kapoor
Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, Uttar Pradesh 226014 India.
Rama Devi
RD
Mittal
BC; BCG immunotherapy; CD44; MIBC; NMIBC