title: Genetic variation in the GSTM3 promoter confer risk and prognosis of renal cell carcinoma by reducing gene expression.
abstract: BACKGROUND
  Glutathione S-transferase mu 3 (GSTM3) has been proven to be downregulated in renal cell carcinoma (RCC). We aimed to characterise the role of GSTM3 and its genetic predisposition on the occurrence and postoperative prognosis of RCC.
  
  
  METHODS
  The effect of GSTM3 on RCC aggressiveness was examined using transfection and silencing methods. Glutathione S-transferase mu 3 expression in renal tissues was examined by immunohistochemistry. The associations of rs1332018 (A-63C) and rs7483 (V224I) polymorphisms with RCC risk were examined using 400 RCC patients and 802 healthy controls. The factors contributing to postoperative disease-specific survival of RCC patients were evaluated using the Cox proportional hazard model.
  
  
  RESULTS
  Glutathione S-transferase mu 3 silencing increased the invasion and anchorage-independent growth of RCC cell lines. rs1332018 (AC+CC vs AA), which correlated with low expression of GSTM3 in kidney, was associated with RCC risk (odds ratio, 1.446; 95% confidence interval (CI), 1.111-1.882). rs1332018 variants and low GSTM3 expression significantly predicted unfavourable postoperative survivals of RCC patients (P<0.05). rs1332018 variants independently predicted a poor prognosis (hazard ratio, 2.119; 95% CI, 1.043-4.307).
  
  
  CONCLUSIONS
  Glutathione S-transferase mu 3 may function as a tumour suppressor in RCC. rs1332018 genetic variants predispose the host to downregulating GSTM3 expression in kidney, facilitate carcinogenesis, and predict an unfavourable postoperative prognosis of RCC.
authors.affiliation: Department of Epidemiology, Second Military Medical University, 800 Xiangyin Road, Shanghai 200433, China.
authors.forename: X
authors.initials: X
authors.lastname: Tan
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Han
authors.forename: W
authors.initials: W
authors.lastname: Chang
authors.forename: T
authors.initials: T
authors.lastname: Su
authors.forename: J
authors.initials: J
authors.lastname: Hou
authors.forename: D
authors.initials: D
authors.lastname: Xu
authors.forename: Y
authors.initials: Y
authors.lastname: Yu
authors.forename: W
authors.initials: W
authors.lastname: Ma
authors.forename: T C
authors.initials: TC
authors.lastname: Thompson
authors.forename: G
authors.initials: G
authors.lastname: Cao
mesh_terms: D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005982:Glutathione Transferase / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D014162:Transfection
chemical_list: C483009:GSTM3 protein, human; D005982:Glutathione Transferase