title: Renal cell carcinoma risk is associated with the interactions of APOE, VHL and MTHFR gene polymorphisms.
abstract: OBJECTIVE
  The study was designed to explore the association of renal cell carcinoma (RCC) with VHL (rs779805), MTHFR (rs1801133) and APOE (rs8106822 and rs405509) polymorphisms, investigate the interactions among the single nucleotide polymorphisms (SNPs), and explore roles of the interactions in the pathogenesis of RCC in Chinese Han population.
  
  
  METHODS
  81 RCC patients and 80 healthy controls were included in the study. Polymerase chain reaction (PCR) and direct sequencing methods were used in the analysis on the genotypes of APOE, VHL and MTHFR gene polymorphisms. Multifactor dimensionality reduction (MDR) method was adopted to conduct gene-gene interaction analysis. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were utilized to evaluate the correlation between gene-gene interactions and RCC risk.
  
  
  RESULTS
  Significant correlations were found between RCC risk and 3 SNPs (rs8106822, rs779805 and rs1801133). Genotype AA and allele A of APOE rs8106822 were significantly associated with RCC susceptibility (OR=2.65, 95% CI=1.05-6.69). Meanwhile, we found that the frequencies of genotype GG and allele G were much higher in case group, compared with controls (P<0.05 for both) and they appeared to be risk factors for RCC (OR=2.90, 95% CI=1.22-6.87; OR=1.78, 95% CI=1.14-2.27). While, allele T of MTHFR rs1801133 could decrease the risk of RCC (OR=0.62, 95% CI=0.40-0.97). MDR analysis showed that gene-gene interactions among APOE, VHL and MTHFR SNPs were closely related with RCC susceptibility.
  
  
  CONCLUSIONS
  APOE, VHL and MTHFR gene polymorphisms were related to the risk of RCC. The interactions among APOE, VHL and MTHFR genes could increase the risk of RCC.
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, China ; Department of Urology, Haikou Municipal Hospital Haikou 570208, Hainan, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Lv
authors.affiliation: Department of Urology, Haikou Municipal Hospital Haikou 570208, Hainan, China.
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Bai
authors.affiliation: Department of Urology, Haikou Municipal Hospital Haikou 570208, Hainan, China.
authors.forename: Zhenxiang
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, China.
authors.forename: Pengcheng
authors.initials: P
authors.lastname: Luo
authors.affiliation: Department of Urology, Renmin Hospital of Wuhan University Wuhan 430060, Hubei, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D001057:Apolipoproteins E / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
chemical_list: D001057:Apolipoproteins E; C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human
keywords: APOE; MTHFR; RCC; VHL; gene-gene interaction; polymorphisms