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A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.

Publication ,  Journal Article
Zhou, K; Hu, D; Lu, J; Fan, W; Liu, H; Chen, H; Chen, G; Wei, Q; Du, G; Mao, Y; Lu, D; Zhou, L
Published in: BMC Cancer
March 23, 2011

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.

Duke Scholars

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

March 23, 2011

Volume

11

Start / End Page

104

Location

England

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Glioblastoma
 

Citation

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Zhou, K., Hu, D., Lu, J., Fan, W., Liu, H., Chen, H., … Zhou, L. (2011). A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population. BMC Cancer, 11, 104. https://doi.org/10.1186/1471-2407-11-104
Zhou, Keke, Dezhi Hu, Juan Lu, Weiwei Fan, Hongliang Liu, Hongyan Chen, Gong Chen, et al. “A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.BMC Cancer 11 (March 23, 2011): 104. https://doi.org/10.1186/1471-2407-11-104.
Zhou K, Hu D, Lu J, Fan W, Liu H, Chen H, et al. A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population. BMC Cancer. 2011 Mar 23;11:104.
Zhou, Keke, et al. “A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population.BMC Cancer, vol. 11, Mar. 2011, p. 104. Pubmed, doi:10.1186/1471-2407-11-104.
Zhou K, Hu D, Lu J, Fan W, Liu H, Chen H, Chen G, Wei Q, Du G, Mao Y, Lu D, Zhou L. A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population. BMC Cancer. 2011 Mar 23;11:104.
Journal cover image

Published In

BMC Cancer

DOI

EISSN

1471-2407

Publication Date

March 23, 2011

Volume

11

Start / End Page

104

Location

England

Related Subject Headings

  • Young Adult
  • Risk Factors
  • Promoter Regions, Genetic
  • Polymorphism, Single Nucleotide
  • Oncology & Carcinogenesis
  • Middle Aged
  • Male
  • Humans
  • High-Throughput Nucleotide Sequencing
  • Glioblastoma