title: GNAS1 (Gαs) gene T393C polymorphism and renal cell carcinoma risk in a North Indian population: a case-control study.
abstract: OBJECTIVE
  Heterotrimeric G protein α-subunit Gαs is required for activation of adenylyl cyclase and generation of cyclic adenosine monophosphate (cAMP) in cells and plays a key role in multiple signal transduction pathways, linked to proapoptotic processes in cancer cells. This study investigated whether Gαs gene polymorphism was associated with increased renal cell carcinoma (RCC) risk in the North Indian population. In the present study, genotyping of GNAS1 gene in 196 RCC cases and 250 healthy controls was performed via polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  The frequency of homozygous genotype CC was 29.6%, heterozygous TC was 51.5%, and homozygous TT was 18.9% in cases, whereas in controls it was 16.8%, 50.8%, and 32.4%, respectively; thus, there was a significant difference between the two groups (p=0.0001) in the univariate model. Further, multivariate analysis also demonstrated significant association of CC genotype with RCC risk (p=0.002). The high-risk genotype CC of GNAS1 gene showed threefold increase in risk to RCC relative to the TT genotype (unadjusted odds ratio [OR]=3.023, 95% confidence interval [CI]: 1.734-5.270). Whereas multivariate analysis showed a twofold increase in RCC risk among the CC genotype compared with the TT genotype (adjusted OR=2.181, 95% CI: 1.344-3.538). The C allele frequency was found to be significantly higher in RCC patients (55.3%) than in controls (42.2%) as compared with the T allele frequency that was 44.64% in RCC cases and 57.8% in controls. Moreover, patients with the CC genotype showed the worst prognosis in terms of the highest frequency of individuals having higher stages of RCC, but did not show any association with histological grade.
  
  
  CONCLUSIONS
  Our results suggest that a T393C SNP could be considered as a genetic marker implicated in the pathogenesis of RCC.
authors.affiliation: Section of Molecular Carcinogenesis and Chemoprevention, Department of Medical Elementology and Toxicology, Faculty of Science, Hamdard University, New Delhi, India.
authors.forename: Wani
authors.initials: W
authors.lastname: Arjumand
authors.forename: Shiekh Tanveer
authors.initials: ST
authors.lastname: Ahmad
authors.forename: Sana
authors.initials: S
authors.lastname: Nafees
authors.forename: Nemat
authors.initials: N
authors.lastname: Ali
authors.forename: Summya
authors.initials: S
authors.lastname: Rashid
authors.forename: Amlesh
authors.initials: A
authors.lastname: Seth
authors.forename: Sarwat
authors.initials: S
authors.lastname: Sultana
mesh_terms: D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D044465:White People / Q000235:genetics*