title: Functional polymorphisms in promoter survivin gene and its association with susceptibility to bladder cancer in North Indian cohort.
abstract: Survivin is a member of novel inhibitor of apoptosis protein family which expressed in human cancers. The molecular detection of bladder cancer by targeting Survivin as a novel marker may be useful in the occurrence and progression of cancer. We genotyped Survivin -31G>C, -1547A>G and -241C>T by PCR-restriction fragment length polymorphism to evaluate the risk of bladder cancer (BC) in 200 BC patients and 200 healthy controls from North Indian cohort. We observed significant increased BC risk associated with variant CC genotype of Survivin -31G>C having 2.6 fold risk. The variant genotype of Survivin -1547A>G was significantly associated with BC risk (P = 0.047). In case of Survivin -241C>T the protective  genotype for BC was heterozygous (P = 0.035). Smoking significantly modulated the risk in patients with Survivin -1547A>G polymorphism. Variant as well as hetero genotype of Survivin -31G>C was associated with reduced risk of recurrence (HR = 0.22 and 0.35) in BC patients receiving BCG treatment thus showing least survival. Furthermore, the haplotype analysis revealed C-A-T haplotype to be associated with reduced BC risk. Our findings suggested that the functional polymorphism -31G>C, -1547A>G and -241C>T in the promoter of Survivin gene may play a significant role in mediating the BC risk among North Indian cohort.
authors.affiliation: Department of Urology and Renal Transplantation, Sanjay Gandhi Post Graduate Institute of Medical Sciences, Raebareli Road, Lucknow, 226014, Uttar Pradesh, India.
authors.forename: Praveen Kumar
authors.initials: PK
authors.lastname: Jaiswal
authors.forename: Apul
authors.initials: A
authors.lastname: Goel
authors.forename: Anil
authors.initials: A
authors.lastname: Mandhani
authors.forename: Rama Devi
authors.initials: RD
authors.lastname: Mittal
mesh_terms: D016022:Case-Control Studies; D015331:Cohort Studies; D003710:Demography; D004843:Epistasis, Genetic; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007167:Immunotherapy; D007194:India; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009163:Mycobacterium bovis; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012008:Recurrence; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects / Q000235:genetics; D000077022:Survivin; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000628:therapy
chemical_list: C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D000077022:Survivin