title: PSCA gene variants (rs2294008 and rs2978974) confer increased susceptibility of gallbladder carcinoma in females.
abstract: OBJECTIVE
  PSCA is a tissue specific tumor suppressor or oncogene which has been found to be associated with several human tumors including gallbladder cancer. It is considered to be involved in the cell-proliferation inhibition and/or cell-death induction activity. Therefore, we aimed to investigate the role of PSCA gene polymorphisms in gallbladder cancer risk in North Indian population.
  
  
  METHODS
  A total of 405 gallbladder cancer patients and 247 healthy controls were included in the case-control study for risk prediction. We examined the association of two functional SNPs, rs2294008 and rs2978974 in PSCA gene by genotyping using Taqman allelic discrimination assays. Statistical analysis was done using SPSS software, version 17. Linkage disequilibrium and haplotype analysis was done with the help of SNPstats software. FDR test was used to correct for multiple comparisons.
  
  
  RESULTS
  No significant associations of rs2294008 and rs2978974 genetic variants of the PSCA gene were found with GBC risk at allele, genotype or haplotype levels. Stratifying the subjects on the basis of gallstone also did not show any significant result. However, on gender stratification, we found a significant association of Trs2294008-Grs2978974 haplotype with higher risk of GBC in females (FDR Pcorr=0.021, OR=1.6). In contrary, Trs2294008-A rs2978974 haplotype conferred significant lower risk in males (FDR Pcorr=0.013; OR=0.25).
  
  
  CONCLUSIONS
  These findings suggest that PSCA genetic variants may have a significant effect on GBC susceptibility in a gender specific manner.
authors.affiliation: Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
authors.forename: Rajani
authors.initials: R
authors.lastname: Rai
authors.forename: Kiran L
authors.initials: KL
authors.lastname: Sharma
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Misra
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D000951:Antigens, Neoplasm / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics; D005704:Gallbladder / Q000378:metabolism / Q000473:pathology; D005706:Gallbladder Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D042882:Gallstones / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D000951:Antigens, Neoplasm; D058851:GPI-Linked Proteins; D009363:Neoplasm Proteins; C110843:PSCA protein, human
keywords: CI; Case–control study; FDR; False discovery rate; GBC; GWAS; Gallbladder cancer (GBC); HC; HWE; Hardy–Weinberg equilibrium; Healthy controls; LD; OR; PSCA; Prostate stem cell antigen; Prostate stem cell antigen (PSCA); SNP; SPSS; Single nucleotide polymorphisms; Tumor suppressor gene; confidence interval; gallbladder cancer; genome-wide association study; linkage disequilibrium; odds ratio; single nucleotide polymorphism; statistical package for social sciences