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

The association of APE1 −656T > G and 1349 T > G polymorphisms and cancer risk: a meta-analysis based on 37 case-control studies

Authors: Bin Zhou, Hailin Shan, Ying Su, Kai Xia, Xiaxia Shao, Weidong Mao, Qing Shao

Published in: BMC Cancer | Issue 1/2011

Login to get access

Abstract

Background

APE1 (apurinic/apyrimidinic endonuclease 1) is an important DNA repair protein in the base excision repair pathway. Polymorphisms in APE1 have been implicated in susceptibility to cancer; however, results from the published studies remained inconclusive. The objective of this study was to conduct a meta-analysis investigating the association between polymorphisms in APE1 and the risk for cancer.

Methods

The PubMed and Embase databases were searched for case-control studies published up to June, 2011 that investigated APE1 polymorphisms and cancer risk. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations.

Results

Two polymorphisms (−656 T > G, rs1760944 and 1349 T > G, rs1130409) in 37 case-control studies including 15, 544 cancer cases and 21, 109 controls were analyzed. Overall, variant genotypes (GG and TG/GG) of −656 T > G polymorphism were associated with significantly decreased cancer risk in homozygote comparison (OR = 0.81, 95%CI: 0.67-0.97), dominant model comparison (OR = 0.89, 95%CI: 0.81-0.97) and recessive model comparison (OR = 0.90, 95%CI: 0.82-0.98), whereas the 1349 T > G polymorphism had no effects on overall cancer risk. In the stratified analyses for −656 T > G polymorphism, there was a significantly decreased risk of lung cancer and among Asian populations.

Conclusions

Although some modest bias could not be eliminated, the meta-analysis suggests that APE1 −656 T > G polymorphism has a possible protective effect on cancer risk particularly among Asian populations whereas 1349 T > G polymorphism does not contribute to the development of cancer.
Appendix
Available only for authorised users
Literature
1.
Pharoah PD, Dunning AM, Ponder BA, Easton DF: Association studies for finding cancer-susceptibility genetic variants. Nat Rev Cancer. 2004, 4 (11): 850-860. 10.1038/nrc1476.CrossRefPubMed
2.
Iscovich J, Howe GR: Cancer incidence patterns (1972-91) among migrants from the Soviet Union to Israel. Cancer Causes Control. 1998, 9 (1): 29-36. 10.1023/A:1008893102428.CrossRefPubMed
3.
Hecht SS: Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention. Lancet Oncol. 2002, 3 (8): 461-469. 10.1016/S1470-2045(02)00815-X.CrossRefPubMed
4.
Hoeijmakers JH: Genome maintenance mechanisms for preventing cancer. Nature. 2001, 411 (6835): 366-374. 10.1038/35077232.CrossRefPubMed
5.
Barzilay G, Hickson ID: Structure and function of apurinic/apyrimidinic endonucleases. Bioessays. 1995, 17 (8): 713-719. 10.1002/bies.950170808.CrossRefPubMed
6.
Tell G, Quadrifoglio F, Tiribelli C, Kelley MR: The many functions of APE1/Ref-1: not only a DNA repair enzyme. Antioxid Redox Signal. 2009, 11 (3): 601-620. 10.1089/ars.2008.2194.CrossRefPubMedPubMedCentral
7.
Izumi T, Hazra TK, Boldogh I, Tomkinson AE, Park MS, Ikeda S, Mitra S: Requirement for human AP endonuclease 1 for repair of 3'-blocking damage at DNA single-strand breaks induced by reactive oxygen species. Carcinogenesis. 2000, 21 (7): 1329-1334. 10.1093/carcin/21.7.1329.CrossRefPubMed
8.
Fortini P, Pascucci B, Parlanti E, D'Errico M, Simonelli V, Dogliotti E: The base excision repair: mechanisms and its relevance for cancer susceptibility. Biochimie. 2003, 85 (11): 1053-1071. 10.1016/j.biochi.2003.11.003.CrossRefPubMed
9.
Bhakat KK, Mantha AK, Mitra S: Transcriptional regulatory functions of mammalian AP-endonuclease (APE1/Ref-1), an essential multifunctional protein. Antioxid Redox Signal. 2009, 11 (3): 621-638. 10.1089/ars.2008.2198.CrossRefPubMedPubMedCentral
10.
Tell G, Fantini D, Quadrifoglio F: Understanding different functions of mammalian AP endonuclease (APE1) as a promising tool for cancer treatment. Cell Mol Life Sci. 2010, 67 (21): 3589-3608. 10.1007/s00018-010-0486-4.CrossRefPubMed
11.
Xi T, Jones IM, Mohrenweiser HW: Many amino acid substitution variants identified in DNA repair genes during human population screenings are predicted to impact protein function. Genomics. 2004, 83 (6): 970-979. 10.1016/j.ygeno.2003.12.016.CrossRefPubMed
12.
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
13.
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
14.
Wang M, Qin C, Zhu J, Yuan L, Fu G, Zhang Z, Yin C: Genetic variants of XRCC1, APE1, and ADPRT genes and risk of bladder cancer. DNA Cell Biol. 2010, 29 (6): 303-311. 10.1089/dna.2009.0969.CrossRefPubMed
15.
Zhou K, Hu D, Lu J, Fan W, Liu H, Chen H, Chen G, Wei Q, Du G, Mao Y, et al: A genetic variant in the APE1/Ref-1 gene promoter -141 T/G may modulate risk of glioblastoma in a Chinese Han population. BMC Cancer. 2011, 11: 104-10.1186/1471-2407-11-104.CrossRefPubMedPubMedCentral
16.
Berndt SI, Huang WY, Fallin MD, Helzlsouer KJ, Platz EA, Weissfeld JL, Church TR, Welch R, Chanock SJ, Hayes RB: Genetic variation in base excision repair genes and the prevalence of advanced colorectal adenoma. Cancer Res. 2007, 67 (3): 1395-1404. 10.1158/0008-5472.CAN-06-1390.CrossRefPubMed
17.
Figueroa JD, Malats N, Real FX, Silverman D, Kogevinas M, Chanock S, Welch R, Dosemeci M, Tardon A, Serra C, et al: Genetic variation in the base excision repair pathway and bladder cancer risk. Hum Genet. 2007, 121 (2): 233-242. 10.1007/s00439-006-0294-y.CrossRefPubMed
18.
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
19.
Au WW, Salama SA, Sierra-Torres CH: Functional characterization of polymorphisms in DNA repair genes using cytogenetic challenge assays. Environ Health Perspect. 2003, 111 (15): 1843-1850. 10.1289/ehp.6632.CrossRefPubMedPubMedCentral
20.
Mantel N, Haenszel W: Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959, 22 (4): 719-748.PubMed
21.
DerSimonian R, Laird N: Meta-analysis in clinical trials. Control Clin Trials. 1986, 7 (3): 177-188. 10.1016/0197-2456(86)90046-2.CrossRefPubMed
22.
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
23.
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
24.
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
25.
Hao B, Wang H, Zhou K, Li Y, Chen X, Zhou G, Zhu Y, Miao X, Tan W, Wei Q, et al: Identification of genetic variants in base excision repair pathway and their associations with risk of esophageal squamous cell carcinoma. Cancer Res. 2004, 64 (12): 4378-4384. 10.1158/0008-5472.CAN-04-0372.CrossRefPubMed
26.
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
27.
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
28.
Moreno V, Gemignani F, Landi S, Gioia-Patricola L, Chabrier A, Blanco I, Gonzalez S, Guino E, Capella G, Canzian F: Polymorphisms in genes of nucleotide and base excision repair: risk and prognosis of colorectal cancer. Clin Cancer Res. 2006, 12 (7 Pt 1): 2101-2108.CrossRefPubMed
29.
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
30.
Terry PD, Umbach DM, Taylor JA: APE1 genotype and risk of bladder cancer: evidence for effect modification by smoking. Int J Cancer. 2006, 118 (12): 3170-3173. 10.1002/ijc.21768.CrossRefPubMed
31.
Wu X, Gu J, Grossman HB, Amos CI, Etzel C, Huang M, Zhang Q, Millikan RE, Lerner S, Dinney CP, et al: Bladder cancer predisposition: a multigenic approach to DNA-repair and cell-cycle-control genes. Am J Hum Genet. 2006, 78 (3): 464-479. 10.1086/500848.CrossRefPubMedPubMedCentral
32.
Zhang Y, Newcomb PA, Egan KM, Titus-Ernstoff L, Chanock S, Welch R, Brinton LA, Lissowska J, Bardin-Mikolajczak A, Peplonska B, et al: Genetic polymorphisms in base-excision repair pathway genes and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2006, 15 (2): 353-358. 10.1158/1055-9965.EPI-05-0653.CrossRefPubMed
33.
Matullo G, Dunning AM, Guarrera S, Baynes C, Polidoro S, Garte S, Autrup H, Malaveille C, Peluso M, Airoldi L, et al: DNA repair polymorphisms and cancer risk in non-smokers in a cohort study. Carcinogenesis. 2006, 27 (5): 997-1007.CrossRefPubMed
34.
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
35.
Li C, Hu Z, Lu J, Liu Z, Wang LE, El-Naggar AK, Sturgis EM, Spitz MR, Wei Q: Genetic polymorphisms in DNA base-excision repair genes ADPRT, XRCC1, and APE1 and the risk of squamous cell carcinoma of the head and neck. Cancer. 2007, 110 (4): 867-875. 10.1002/cncr.22861.CrossRefPubMed
36.
Andrew AS, Karagas MR, Nelson HH, Guarrera S, Polidoro S, Gamberini S, Sacerdote C, Moore JH, Kelsey KT, Demidenko E, et al: DNA repair polymorphisms modify bladder cancer risk: a multi-factor analytic strategy. Hum Hered. 2008, 65 (2): 105-118. 10.1159/000108942.CrossRefPubMed
37.
Pardini B, Naccarati A, Novotny J, Smerhovsky Z, Vodickova L, Polakova V, Hanova M, Slyskova J, Tulupova E, Kumar R, et al: DNA repair genetic polymorphisms and risk of colorectal cancer in the Czech Republic. Mutat Res. 2008, 638 (1-2): 146-153. 10.1016/j.mrfmmm.2007.09.008.CrossRefPubMed
38.
Tse D, Zhai R, Zhou W, Heist RS, Asomaning K, Su L, Lynch TJ, Wain JC, Christiani DC, Liu G: Polymorphisms of the NER pathway genes, ERCC1 and XPD are associated with esophageal adenocarcinoma risk. Cancer Causes Control. 2008, 19 (10): 1077-1083. 10.1007/s10552-008-9171-4.CrossRefPubMedPubMedCentral
39.
Huang WY, Gao YT, Rashid A, Sakoda LC, Deng J, Shen MC, Wang BS, Han TQ, Zhang BH, Chen BE, et al: Selected base excision repair gene polymorphisms and susceptibility to biliary tract cancer and biliary stones: a population-based case-control study in China. Carcinogenesis. 2008, 29 (1): 100-105.CrossRefPubMed
40.
Chiang FY, Wu CW, Hsiao PJ, Kuo WR, Lee KW, Lin JC, Liao YC, Juo SH: Association between polymorphisms in DNA base excision repair genes XRCC1, APE1, and ADPRT and differentiated thyroid carcinoma. Clin Cancer Res. 2008, 14 (18): 5919-5924. 10.1158/1078-0432.CCR-08-0906.CrossRefPubMed
41.
Smith TR, Levine EA, Freimanis RI, Akman SA, Allen GO, Hoang KN, Liu-Mares W, Hu JJ: Polygenic model of DNA repair genetic polymorphisms in human breast cancer risk. Carcinogenesis. 2008, 29 (11): 2132-2138. 10.1093/carcin/bgn193.CrossRefPubMedPubMedCentral
42.
Gangwar R, Ahirwar D, Mandhani A, Mittal RD: Influence of XPD and APE1 DNA repair gene polymorphism on bladder cancer susceptibility in north India. Urology. 2009, 73 (3): 675-680. 10.1016/j.urology.2008.09.043.CrossRefPubMed
43.
Agachan B, Kucukhuseyin O, Aksoy P, Turna A, Yaylim I, Gormus U, Ergen A, Zeybek U, Dalan B, Isbir T: Apurinic/apyrimidinic endonuclease (APE1) gene polymorphisms and lung cancer risk in relation to tobacco smoking. Anticancer Res. 2009, 29 (6): 2417-2420.PubMed
44.
Deng Q, Sheng L, Su D, Zhang L, Liu P, Lu K, Ma S: Genetic polymorphisms in ATM, ERCC1, APE1 and iASPP genes and lung cancer risk in a population of southeast China. Med Oncol. 2011, 28 (3): 667-672. 10.1007/s12032-010-9507-2.CrossRefPubMed
45.
Palli D, Polidoro S, D'Errico M, Saieva C, Guarrera S, Calcagnile AS, Sera F, Allione A, Gemma S, Zanna I, et al: Polymorphic DNA repair and metabolic genes: a multigenic study on gastric cancer. Mutagenesis. 2010, 25 (6): 569-575. 10.1093/mutage/geq042.CrossRefPubMed
46.
Jelonek K, Gdowicz-Klosok A, Pietrowska M, Borkowska M, Korfanty J, Rzeszowska-Wolny J, Widlak P: Association between single-nucleotide polymorphisms of selected genes involved in the response to DNA damage and risk of colon, head and neck, and breast cancers in a Polish population. J Appl Genet. 2010, 51 (3): 343-352. 10.1007/BF03208865.CrossRefPubMed
47.
Cao Q, Qin C, Meng X, Ju X, Ding Q, Wang M, Zhu J, Wang W, Li P, Chen J, et al: Genetic polymorphisms in APE1 are associated with renal cell carcinoma risk in a chinese population. Mol Carcinog. 2011, 50 (11): 863-870. 10.1002/mc.20791.CrossRefPubMed
48.
Duval S, Tweedie R: Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics. 2000, 56 (2): 455-463. 10.1111/j.0006-341X.2000.00455.x.CrossRefPubMed
49.
50.
Hu JJ, Smith TR, Miller MS, Lohman K, Case LD: Genetic regulation of ionizing radiation sensitivity and breast cancer risk. Environ Mol Mutagen. 2002, 39 (2-3): 208-215. 10.1002/em.10058.CrossRefPubMed
51.
Gu D, Wang M, Zhang Z, Chen J: The DNA repair gene APE1 T1349G polymorphism and cancer risk: a meta-analysis of 27 case-control studies. Mutagenesis. 2009, 24 (6): 507-512. 10.1093/mutage/gep036.CrossRefPubMed
52.
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.CrossRefPubMed
53.
De Ruyck K, Szaumkessel M, De Rudder I, Dehoorne A, Vral A, Claes K, Velghe A, Van Meerbeeck J, Thierens H: Polymorphisms in base-excision repair and nucleotide-excision repair genes in relation to lung cancer risk. Mutat Res. 2007, 631 (2): 101-110.CrossRefPubMed
54.
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
Metadata
Title
The association of APE1 −656T > G and 1349 T > G polymorphisms and cancer risk: a meta-analysis based on 37 case-control studies
Authors
Bin Zhou
Hailin Shan
Ying Su
Kai Xia
Xiaxia Shao
Weidong Mao
Qing Shao
Publication date
01-12-2011
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2011
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-11-521

Other articles of this Issue 1/2011

BMC Cancer 1/2011 Go to the issue

Research article

Safety, feasibility and effects of an individualised walking intervention for women undergoing chemotherapy for ovarian cancer: a pilot study

Research article

Involvement of promoter methylation in the regulation of Pregnane X receptor in colon cancer cells

Study protocol

Neo-adjuvant chemotherapy followed by surgery and chemotherapy or by surgery and chemoradiotherapy for patients with resectable gastric cancer (CRITICS)

Research article

Sentinel lymph node biopsy is unsuitable for routine practice in younger female patients with unilateral low-risk papillary thyroid carcinoma

Research article

Genome-wide expression patterns associated with oncogenesis and sarcomatous transdifferentation of cholangiocarcinoma

Research article

The relative risk of second primary cancers in Queensland, Australia: a retrospective cohort study
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