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

• Main Authors: Wei Qingyi, Du Guhong, Chen Gong, Chen Hongyan, Liu Hongliang, Fan Weiwei, Lu Juan, Hu Dezhi, Zhou Keke, Mao Ying, Lu Daru, Zhou Liangfu
• Format: Article
• Language: English
• Published: BMC 2011-03-01
• Series: BMC Cancer
• Subjects: DNA repair; glioma; APE1/Ref-1; association study; false positive report probability
• Online Access: http://www.biomedcentral.com/1471-2407/11/104

<p>Abstract</p> <p>Background</p> <p>The human apurinic/apyrimidinic endonuclease 1/Redox effector factor-1 (<it>APE1/Ref-1</it>) is implicated in tumor development and progression. Recently, the <it>APE1/Ref-1 </it>promoter -141T/G variant (rs1760944) has been reported to be associated with lung cancer risk. Given the importance of <it>APE1/Ref-1 </it>in both DNA repair and redox activity, we speculate that the -141T/G polymorphism may confer individual susceptibility to gliomas or its subtypes.</p> <p>Methods</p> <p>The <it>APE1/Ref-1 </it>-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.</p> <p>Results</p> <p>The significant association between the <it>APE1/Ref-1 </it>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, <it>P </it>= 0.032). Individuals with the homozygous -141GG genotype exhibited 46% reduced risk of glioblastoma (adjusted OR = 0.54, 95% CI 0.34-0.87, <it>P </it>= 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 <it>P-</it>associated with the trend test was 0.014.</p> <p>Conclusions</p> <p>Our results suggest that a specific genetic variant located in the <it>APE1/Ref-1 </it>promoter may modulate risk of glioblastoma, but not for other histological gliomas. Larger studies with more <it>APE1 </it>polymorphisms are required to validate these preliminary findings.</p>