Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

Keynote webinar | Spotlight on medication adherence

LIVE: Thursday 27th June 2024, 18:00-19:30 (CEST)
Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.
ADVANCED SEARCH
Log in
Top
BMC Cancer
Published in: BMC Cancer 1/2011

Open Access 01-12-2011 | Research article

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

Authors: Keke Zhou, Dezhi Hu, Juan Lu, Weiwei Fan, Hongliang Liu, Hongyan Chen, Gong Chen, Qingyi Wei, Guhong Du, Ying Mao, Daru Lu, Liangfu Zhou

Published in: BMC Cancer | Issue 1/2011

Login to get access

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.
Literature
1.
Xue QC, Pu PY, Yang YS, Shen CH: A survey of 790 cases of astrocytoma. Clin Neurol Neurosurg. 1990, 92 (1): 27-33. 10.1016/0303-8467(90)90004-O.CrossRefPubMed
2.
Ohgaki H, Kleihues P: Epidemiology and etiology of gliomas. Acta Neuropathol. 2005, 109 (1): 93-108. 10.1007/s00401-005-0991-y.CrossRefPubMed
3.
Van Meir EG, Hadjipanayis CG, Norden AD, Shu HK, Wen PY, Olson JJ: Exciting new advances in neuro-oncology: the avenue to a cure for malignant glioma. CA Cancer J Clin. 2010, 60 (3): 166-193. 10.3322/caac.20069.CrossRefPubMedPubMedCentral
4.
Fishel ML, Kelley MR: The DNA base excision repair protein Ape1/Ref-1 as a therapeutic and chemopreventive target. Mol Aspects Med. 2007, 28 (3-4): 375-395. 10.1016/j.mam.2007.04.005.CrossRefPubMed
5.
Demple B, Harrison L: Repair of oxidative damage to DNA: enzymology and biology. Annu Rev Biochem. 1994, 63: 915-948. 10.1146/annurev.bi.63.070194.004411.CrossRefPubMed
6.
7.
Wilson DM, Barsky D: The major human abasic endonuclease: formation, consequences and repair of abasic lesions in DNA. Mutat Res. 2001, 485 (4): 283-307.CrossRefPubMed
8.
Xu YJ, Kim EY, Demple B: Excision of C-4'-oxidized deoxyribose lesions from double-stranded DNA by human apurinic/apyrimidinic endonuclease (Ape1 protein) and DNA polymerase beta. J Biol Chem. 1998, 273 (44): 28837-28844. 10.1074/jbc.273.44.28837.CrossRefPubMed
9.
Chou KM, Kukhanova M, Cheng YC: A novel action of human apurinic/apyrimidinic endonuclease: excision of L-configuration deoxyribonucleoside analogs from the 3' termini of DNA. J Biol Chem. 2000, 275 (40): 31009-31015. 10.1074/jbc.M004082200.CrossRefPubMed
10.
Chou KM, Cheng YC: An exonucleolytic activity of human apurinic/apyrimidinic endonuclease on 3' mispaired DNA. Nature. 2002, 415 (6872): 655-659. 10.1038/415655a.CrossRefPubMed
11.
Tell G, Damante G, Caldwell D, Kelley MR: The intracellular localization of APE1/Ref-1: more than a passive phenomenon?. Antioxid Redox Signal. 2005, 7 (3-4): 367-384. 10.1089/ars.2005.7.367.CrossRefPubMed
12.
Ludwig DL, MacInnes MA, Takiguchi Y, Purtymun PE, Henrie M, Flannery M, Meneses J, Pedersen RA, Chen DJ: A murine AP-endonuclease gene-targeted deficiency with post-implantation embryonic progression and ionizing radiation sensitivity. Mutat Res. 1998, 409 (1): 17-29.CrossRefPubMed
13.
14.
Hadi MZ, Coleman MA, Fidelis K, Mohrenweiser HW, Wilson DM: Functional characterization of Ape1 variants identified in the human population. Nucleic Acids Res. 2000, 28 (20): 3871-3879. 10.1093/nar/28.20.3871.CrossRefPubMedPubMedCentral
15.
Hu JJ, Smith TR, Miller MS, Mohrenweiser HW, Golden A, Case LD: Amino acid substitution variants of APE1 and XRCC1 genes associated with ionizing radiation sensitivity. Carcinogenesis. 2001, 22 (6): 917-922. 10.1093/carcin/22.6.917.CrossRefPubMed
16.
Mitra AK, Singh N, Singh A, Garg VK, Agarwal A, Sharma M, Chaturvedi R, Rath SK: Association of polymorphisms in base excision repair genes with the risk of breast cancer: a case-control study in North Indian women. Oncol Res. 2008, 17 (3): 127-135.PubMed
17.
Canbay E, Agachan B, Gulluoglu M, Isbir T, Balik E, Yamaner S, Bulut T, Cacina C, Eraltan IY, Yilmaz A, et al: Possible associations of APE1 polymorphism with susceptibility and HOGG1 polymorphism with prognosis in gastric cancer. Anticancer Res. 2010, 30 (4): 1359-1364.PubMed
18.
Li C, Liu Z, Wang LE, Strom SS, Lee JE, Gershenwald JE, Ross MI, Mansfield PF, Cormier JN, Prieto VG, et al: Genetic variants of the ADPRT, XRCC1 and APE1 genes and risk of cutaneous melanoma. Carcinogenesis. 2006, 27 (9): 1894-1901. 10.1093/carcin/bgl042.CrossRefPubMed
19.
Liu Y, Scheurer ME, El-Zein R, Cao Y, Do KA, Gilbert M, Aldape KD, Wei Q, Etzel C, Bondy ML: Association and interactions between DNA repair gene polymorphisms and adult glioma. Cancer Epidemiol Biomarkers Prev. 2009, 18 (1): 204-214. 10.1158/1055-9965.EPI-08-0632.CrossRefPubMedPubMedCentral
20.
Chen L, Ambrosone CB, Lee J, Sellers TA, Pow-Sang J, Park JY: Association between polymorphisms in the DNA repair genes XRCC1 and APE1, and the risk of prostate cancer in white and black Americans. J Urol. 2006, 175 (1): 108-112. 10.1016/S0022-5347(05)00042-X. discussion 112CrossRefPubMed
21.
Jiao L, Bondy ML, Hassan MM, Wolff RA, Evans DB, Abbruzzese JL, Li D: Selected polymorphisms of DNA repair genes and risk of pancreatic cancer. Cancer Detect Prev. 2006, 30 (3): 284-291. 10.1016/j.cdp.2006.05.002.CrossRefPubMed
22.
McKean-Cowdin R, Barnholtz-Sloan J, Inskip PD, Ruder AM, Butler M, Rajaraman P, Razavi P, Patoka J, Wiencke JK, Bondy ML, et al: Associations between polymorphisms in DNA repair genes and glioblastoma. Cancer Epidemiol Biomarkers Prev. 2009, 18 (4): 1118-1126. 10.1158/1055-9965.EPI-08-1078.CrossRefPubMedPubMedCentral
23.
Shen M, Berndt SI, Rothman N, Mumford JL, He X, Yeager M, Welch R, Chanock S, Keohavong P, Donahue M, et al: Polymorphisms in the DNA base excision repair genes APEX1 and XRCC1 and lung cancer risk in Xuan Wei, China. Anticancer Res. 2005, 25 (1B): 537-542.PubMed
24.
Misra RR, Ratnasinghe D, Tangrea JA, Virtamo J, Andersen MR, Barrett M, Taylor PR, Albanes D: Polymorphisms in the DNA repair genes XPD, XRCC1, XRCC3, and APE/ref-1, and the risk of lung cancer among male smokers in Finland. Cancer Lett. 2003, 191 (2): 171-178. 10.1016/S0304-3835(02)00638-9.CrossRefPubMed
25.
Ito H, Matsuo K, Hamajima N, Mitsudomi T, Sugiura T, Saito T, Yasue T, Lee KM, Kang D, Yoo KY, et al: Gene-environment interactions between the smoking habit and polymorphisms in the DNA repair genes, APE1 Asp148Glu and XRCC1 Arg399Gln, in Japanese lung cancer risk. Carcinogenesis. 2004, 25 (8): 1395-1401. 10.1093/carcin/bgh153.CrossRefPubMed
26.
Popanda O, Schattenberg T, Phong CT, Butkiewicz D, Risch A, Edler L, Kayser K, Dienemann H, Schulz V, Drings P, et al: Specific combinations of DNA repair gene variants and increased risk for non-small cell lung cancer. Carcinogenesis. 2004, 25 (12): 2433-2441. 10.1093/carcin/bgh264.CrossRefPubMed
27.
Zienolddiny S, Campa D, Lind H, Ryberg D, Skaug V, Stangeland L, Phillips DH, Canzian F, Haugen A: Polymorphisms of DNA repair genes and risk of non-small cell lung cancer. Carcinogenesis. 2006, 27 (3): 560-567. 10.1093/carcin/bgi232.CrossRefPubMed
28.
Lo YL, Jou YS, Hsiao CF, Chang GC, Tsai YH, Su WC, Chen KY, Chen YM, Huang MS, Hu CY, et al: A polymorphism in the APE1 gene promoter is associated with lung cancer risk. Cancer Epidemiol Biomarkers Prev. 2009, 18 (1): 223-229. 10.1158/1055-9965.EPI-08-0749.CrossRefPubMed
29.
Lu J, Zhang S, Chen D, Wang H, Wu W, Wang X, Lei Y, Wang J, Qian J, Fan W, et al: Functional characterization of a promoter polymorphism in APE1/Ref-1 that contributes to reduced lung cancer susceptibility. FASEB J. 2009, 23 (10): 3459-3469. 10.1096/fj.09-136549.CrossRefPubMed
30.
Wang C, Mao Y, Zhu JH, Zhou LF: The Department of Neurosurgery at Shanghai Huashan Hospital. Neurosurgery. 2008, 62 (4): 947-952. 10.1227/01.neu.0000318181.80040.99. discussion 952-943CrossRefPubMed
31.
Jurinke C, van den Boom D, Cantor CR, Koster H: Automated genotyping using the DNA MassArray technology. Methods Mol Biol. 2002, 187: 179-192.PubMed
32.
Wacholder S, Chanock S, Garcia-Closas M, El Ghormli L, Rothman N: Assessing the probability that a positive report is false: an approach for molecular epidemiology studies. J Natl Cancer Inst. 2004, 96 (6): 434-442. 10.1093/jnci/djh075.CrossRefPubMed
33.
Shete S, Hosking FJ, Robertson LB, Dobbins SE, Sanson M, Malmer B, Simon M, Marie Y, Boisselier B, Delattre JY, et al: Genome-wide association study identifies five susceptibility loci for glioma. Nat Genet. 2009, 41 (8): 899-904. 10.1038/ng.407.CrossRefPubMedPubMedCentral
34.
Simon M, Hosking FJ, Marie Y, Gousias K, Boisselier B, Carpentier C, Schramm J, Mokhtari K, Hoang-Xuan K, Idbaih A, et al: Genetic risk profiles identify different molecular etiologies for glioma. Clin Cancer Res. 2010, 16 (21): 5252-5259. 10.1158/1078-0432.CCR-10-1502.CrossRefPubMedPubMedCentral
35.
Fishel ML, He Y, Reed AM, Chin-Sinex H, Hutchins GD, Mendonca MS, Kelley MR: Knockdown of the DNA repair and redox signaling protein Ape1/Ref-1 blocks ovarian cancer cell and tumor growth. DNA Repair (Amst). 2008, 7 (2): 177-186. 10.1016/j.dnarep.2007.09.008.CrossRef
36.
Luo M, Delaplane S, Jiang A, Reed A, He Y, Fishel M, Nyland RL, Borch RF, Qiao X, Georgiadis MM, et al: Role of the multifunctional DNA repair and redox signaling protein Ape1/Ref-1 in cancer and endothelial cells: small-molecule inhibition of the redox function of Ape1. Antioxid Redox Signal. 2008, 10 (11): 1853-1867. 10.1089/ars.2008.2120.CrossRefPubMedPubMedCentral
37.
Zou GM, Maitra A: Small-molecule inhibitor of the AP endonuclease 1/REF-1 E3330 inhibits pancreatic cancer cell growth and migration. Mol Cancer Ther. 2008, 7 (7): 2012-2021. 10.1158/1535-7163.MCT-08-0113.CrossRefPubMedPubMedCentral
38.
Bobola MS, Blank A, Berger MS, Stevens BA, Silber JR: Apurinic/apyrimidinic endonuclease activity is elevated in human adult gliomas. Clin Cancer Res. 2001, 7 (11): 3510-3518.PubMed
39.
Wilkie GS, Dickson KS, Gray NK: Regulation of mRNA translation by 5'- and 3'-UTR-binding factors. Trends Biochem Sci. 2003, 28 (4): 182-188. 10.1016/S0968-0004(03)00051-3.CrossRefPubMed
40.
De Gobbi M, Viprakasit V, Hughes JR, Fisher C, Buckle VJ, Ayyub H, Gibbons RJ, Vernimmen D, Yoshinaga Y, de Jong P, et al: A regulatory SNP causes a human genetic disease by creating a new transcriptional promoter. Science. 2006, 312 (5777): 1215-1217. 10.1126/science.1126431.CrossRefPubMed
41.
Buckland PR: The importance and identification of regulatory polymorphisms and their mechanisms of action. Biochim Biophys Acta. 2006, 1762 (1): 17-28.CrossRefPubMed
42.
Rajaraman P, Hutchinson A, Wichner S, Black PM, Fine HA, Loeffler JS, Selker RG, Shapiro WR, Rothman N, Linet MS, et al: DNA repair gene polymorphisms and risk of adult meningioma, glioma, and acoustic neuroma. Neuro Oncol. 2010, 12 (1): 37-48.CrossRefPubMed
43.
Zhou K, Liu Y, Zhang H, Liu H, Fan W, Zhong Y, Xu Z, Jin L, Wei Q, Huang F, et al: XRCC3 haplotypes and risk of gliomas in a Chinese population: a hospital-based case-control study. Int J Cancer. 2009, 124 (12): 2948-2953. 10.1002/ijc.24307.CrossRefPubMed
44.
Liu Y, Zhou K, Zhang H, Shugart YY, Chen L, Xu Z, Zhong Y, Liu H, Jin L, Wei Q, et al: Polymorphisms of LIG4 and XRCC4 involved in the NHEJ pathway interact to modify risk of glioma. Hum Mutat. 2008, 29 (3): 381-389. 10.1002/humu.20645.CrossRefPubMed
45.
Wrensch M, Kelsey KT, Liu M, Miike R, Moghadassi M, Sison JD, Aldape K, McMillan A, Wiemels J, Wiencke JK: ERCC1 and ERCC2 polymorphisms and adult glioma. Neuro Oncol. 2005, 7 (4): 495-507. 10.1215/S1152851705000037.CrossRefPubMedPubMedCentral
46.
Yang P, Kollmeyer TM, Buckner K, Bamlet W, Ballman KV, Jenkins RB: Polymorphisms in GLTSCR1 and ERCC2 are associated with the development of oligodendrogliomas. Cancer. 2005, 103 (11): 2363-2372. 10.1002/cncr.21028.CrossRefPubMed
47.
Wang LE, Bondy ML, Shen H, El-Zein R, Aldape K, Cao Y, Pudavalli V, Levin VA, Yung WK, Wei Q: Polymorphisms of DNA repair genes and risk of glioma. Cancer Res. 2004, 64 (16): 5560-5563. 10.1158/0008-5472.CAN-03-2181.CrossRefPubMed
48.
Liu Y, Shete S, Etzel CJ, Scheurer M, Alexiou G, Armstrong G, Tsavachidis S, Liang FW, Gilbert M, Aldape K, et al: Polymorphisms of LIG4, BTBD2, HMGA2, and RTEL1 genes involved in the double-strand break repair pathway predict glioblastoma survival. J Clin Oncol. 2010, 28 (14): 2467-2474. 10.1200/JCO.2009.26.6213.CrossRefPubMedPubMedCentral
49.
Wrensch M, Jenkins RB, Chang JS, Yeh RF, Xiao Y, Decker PA, Ballman KV, Berger M, Buckner JC, Chang S, et al: Variants in the CDKN2B and RTEL1 regions are associated with high-grade glioma susceptibility. Nat Genet. 2009, 41 (8): 905-908. 10.1038/ng.408.CrossRefPubMedPubMedCentral
Metadata
Title
A genetic variant in the APE1/Ref-1 gene promoter -141T/G may modulate risk of glioblastoma in a Chinese Han population
Authors
Keke Zhou
Dezhi Hu
Juan Lu
Weiwei Fan
Hongliang Liu
Hongyan Chen
Gong Chen
Qingyi Wei
Guhong Du
Ying Mao
Daru Lu
Liangfu Zhou
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-104

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue

Research article

Multicenter retrospective analysis of 581 patients with primary intestinal non-hodgkin lymphoma from the Consortium for Improving Survival of Lymphoma (CISL)

Research article

G protein-coupled receptor kinase 5 mediates Tazarotene-induced gene 1-induced growth suppression of human colon cancer cells

Research article

Highly frequent promoter methylation and PIK3CA amplification in non-small cell lung cancer (NSCLC)

Research article

The synthetic peptide P111-136 derived from the C-terminal domain of heparin affin regulatory peptide inhibits tumour growth of prostate cancer PC-3 cells

Research article

Support vector machine model for diagnosis of lymph node metastasis in gastric cancer with multidetector computed tomography: a preliminary study

Research article

Quality of life assessment as a predictor of survival in non-small cell lung cancer
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits