title: A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.
abstract: BACKGROUND
  The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (APE1/Ref-1) is implicated in tumor development and progression. Recently, the APE1/Ref-1 promoter -141T/G variant (rs1760944) has been reported to be associated with lung cancer risk. Given the importance of APE1/Ref-1 in both DNA repair and redox activity, we speculate that the -141T/G polymorphism may confer individual susceptibility to gliomas or its subtypes.
  
  
  METHODS
  The APE1/Ref-1 -141T/G polymorphism was analyzed in a case-control study including 766 glioma patients (among them 241 glioblastoma, 284 astrocytomas except for glioblastoma and 241 other gliomas) and 824 cancer-free controls from eastern China. Genotyping was performed with Sequenom MassARRAY iPLEX platform by use of allele-specific MALDI-TOF mass spectrometry assay. We estimated odds ratios (ORs) and 95% confidence intervals (95% CIs) using unconditional logistic regression. A test of trend was calculated using the genotype as an ordinal variable in the regression model. For each statistically significant association identified, we estimated the false positive reporting probability (FPRP). FPRP values less than 0.2 were consider to indicate robust associations.
  
  
  RESULTS
  The significant association between the APE1/Ref-1 promoter -141T/G polymorphism and glioma risk was not observed. However, the stratified analysis by histology revealed the variant allele G significantly decreased glioblastoma risk (OR = 0.80, 95% CI = 0.65-0.98, P = 0.032). Individuals with the homozygous -141GG genotype exhibited 46% reduced risk of glioblastoma (adjusted OR = 0.54, 95% CI 0.34-0.87, P = 0.012), compared with the TT homozygote. This result remained robust given the prior probabilities of 25% (FPRP = 0.052) and 10% (FPRP = 0.140), but not with a prior probability of 1% (FPRP = 0.643). The P-associated with the trend test was 0.014.
  
  
  CONCLUSIONS
  Our results suggest that a specific genetic variant located in the APE1/Ref-1 promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more APE1 polymorphisms are required to validate these preliminary findings.
authors.affiliation: Neurosurgery Department of Huashan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Keke
authors.initials: K
authors.lastname: Zhou
authors.forename: Dezhi
authors.initials: D
authors.lastname: Hu
authors.forename: Juan
authors.initials: J
authors.lastname: Lu
authors.forename: Weiwei
authors.initials: W
authors.lastname: Fan
authors.forename: Hongliang
authors.initials: H
authors.lastname: Liu
authors.forename: Hongyan
authors.initials: H
authors.lastname: Chen
authors.forename: Gong
authors.initials: G
authors.lastname: Chen
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Wei
authors.forename: Guhong
authors.initials: G
authors.lastname: Du
authors.forename: Ying
authors.initials: Y
authors.lastname: Mao
authors.forename: Daru
authors.initials: D
authors.lastname: Lu
authors.forename: Liangfu
authors.initials: L
authors.lastname: Zhou
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics*; D001932:Brain Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000235:genetics* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D005828:Genetics, Population; D005838:Genotype; D005909:Glioblastoma / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000502:physiology; D011401:Promoter Regions, Genetic / Q000235:genetics* / Q000502:physiology; D012307:Risk Factors; D055815:Young Adult
chemical_list: C085108:APEX1 protein, human; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase