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Published in: Cancer Cell International 1/2015

Open Access 01-12-2015 | Primary research

AXIN2 rs2240308 polymorphism contributes to increased cancer risk: evidence based on a meta-analysis

Authors: Zhitong Wu, Yifan Sun, Shifu Tang, Chunming Liu, Shengbo Zhu, Lili Wei, Hong Xu

Published in: Cancer Cell International | Issue 1/2015

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Abstract

Background

Variants in the axis inhibition 2 (AXIN2) gene might alter the protein’s structure or function or create a multiprotein destruction complex in the Wnt signaling pathway and thus affect an individual’s susceptibility to cancer. The objective of this study is to evaluate broadly the evidence available for the AXIN2 rs2240308 polymorphism and risk of cancer.

Methods

A comprehensive literature search was undertaken for eligible studies in Embase, PubMed, and Cochrane Library up to Nov 30, 2014. Odds ratios (ORs) and the corresponding 95 % confidence intervals (CIs) were used to measure the strength of the models.

Results

Eight articles (10 case-control studies with 1,502 cases and 1,590 controls) were included in this analysis. Overall, the AXIN2 rs2240308 polymorphism was associated with a significant increase in the risk of cancer (G allele vs. A allele: OR = 1.21, 95 % CI = 1.05–1.40, I 2  = 39.5 % and P Q  = 0.094 for heterogeneity; GG vs. AA: OR = 1.30, 95 % CI = 1.04–1.63, I 2  = 35.9 % and P Q  = 0.121 for heterogeneity; GG vs. GA + AA: OR = 1.36, 95 % CI = 1.17–1.58, I 2  = 19.5 % and P Q  = 0.263 for heterogeneity). Asian populations showed similar results. Stratified analysis by cancer types indicated that the AXIN2 rs2240308 polymorphism increases the risk of lung cancer (G allele vs. A allele: OR = 1.36, 95 % CI = 1.17–1.59; GA vs. AA: OR = 1.43, 95 % CI = 1.01–2.02; GG vs. AA: OR = 1.93, 95 % CI = 1.36–2.75; GG + GA vs. AA: OR = 1.65, 95 % CI = 1.18–2.30; GG vs. GA + AA: OR = 1.45, 95 % CI = 1.18–1.79. All I 2  < 50 % and P Q  > 0.100 for heterogeneity).

Conclusions

This study showed that the AXIN2 rs2240308 polymorphism contribute to increasing the risk of cancer, especially lung cancer in Asian populations.
Appendix
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Literature
2.
go back to reference He Y, Liu Z, Qiao C, Xu M, Yu J, Li G. Expression and significance of Wnt signaling components and their target genes in breast carcinoma. Mol Med Rep. 2014;9(1):137–43.PubMed He Y, Liu Z, Qiao C, Xu M, Yu J, Li G. Expression and significance of Wnt signaling components and their target genes in breast carcinoma. Mol Med Rep. 2014;9(1):137–43.PubMed
3.
go back to reference Schaal U, Grenz S, Merkel S, Rau TT, Hadjihannas MV, Kremmer E, et al. Expression and localization of axin 2 in colorectal carcinoma and its clinical implication. Int J Color Dis. 2013;28(11):1469–78.CrossRef Schaal U, Grenz S, Merkel S, Rau TT, Hadjihannas MV, Kremmer E, et al. Expression and localization of axin 2 in colorectal carcinoma and its clinical implication. Int J Color Dis. 2013;28(11):1469–78.CrossRef
4.
go back to reference Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, et al. Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science (New York, NY). 1998;280(5363):596–9.CrossRef Behrens J, Jerchow BA, Wurtele M, Grimm J, Asbrand C, Wirtz R, et al. Functional interaction of an axin homolog, conductin, with beta-catenin, APC, and GSK3beta. Science (New York, NY). 1998;280(5363):596–9.CrossRef
5.
go back to reference Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P. Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3β. Curr Biol. 1998;8(10):573–81.PubMedCrossRef Hart MJ, de los Santos R, Albert IN, Rubinfeld B, Polakis P. Downregulation of β-catenin by human Axin and its association with the APC tumor suppressor, β-catenin and GSK3β. Curr Biol. 1998;8(10):573–81.PubMedCrossRef
6.
go back to reference Xu H-T, Wang L, Lin D, Liu Y, Liu N, Yuan X-M, et al. Abnormal β-Catenin and Reduced Axin Expression Are Associated With Poor Differentiation and Progression in Non–Small Cell Lung Cancer. Am J Clin Pathol. 2006;125(4):534–41.PubMedCrossRef Xu H-T, Wang L, Lin D, Liu Y, Liu N, Yuan X-M, et al. Abnormal β-Catenin and Reduced Axin Expression Are Associated With Poor Differentiation and Progression in Non–Small Cell Lung Cancer. Am J Clin Pathol. 2006;125(4):534–41.PubMedCrossRef
7.
go back to reference Dong X, Seelan RS, Qian C, Mai M, Liu W. Genomic structure, chromosome mapping and expression analysis of the human AXIN2 gene. Cytogenet Cell Genet. 2001;93(1-2):26–8.PubMedCrossRef Dong X, Seelan RS, Qian C, Mai M, Liu W. Genomic structure, chromosome mapping and expression analysis of the human AXIN2 gene. Cytogenet Cell Genet. 2001;93(1-2):26–8.PubMedCrossRef
8.
go back to reference Liu W, Dong X, Mai M, Seelan RS, Taniguchi K, Krishnadath KK, et al. Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling. Nat Genet. 2000;26(2):146–7.PubMedCrossRef Liu W, Dong X, Mai M, Seelan RS, Taniguchi K, Krishnadath KK, et al. Mutations in AXIN2 cause colorectal cancer with defective mismatch repair by activating beta-catenin/TCF signalling. Nat Genet. 2000;26(2):146–7.PubMedCrossRef
9.
go back to reference Wang X, Goode EL, Fredericksen ZS, Vierkant RA, Pankratz VS, Liu-Mares W, et al. Association of genetic variation in genes implicated in the beta-catenin destruction complex with risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17(8):2101–8.PubMedCentralPubMedCrossRef Wang X, Goode EL, Fredericksen ZS, Vierkant RA, Pankratz VS, Liu-Mares W, et al. Association of genetic variation in genes implicated in the beta-catenin destruction complex with risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2008;17(8):2101–8.PubMedCentralPubMedCrossRef
10.
go back to reference Gunes EG, Pinarbasi E, Pinarbasi H. AXIN2 polymorphism and its association with astrocytoma in a Turkish population. Mol Med Rep. 2010;3(4):705–9.PubMed Gunes EG, Pinarbasi E, Pinarbasi H. AXIN2 polymorphism and its association with astrocytoma in a Turkish population. Mol Med Rep. 2010;3(4):705–9.PubMed
11.
go back to reference Liu D, Li L, Yang Y, Liu W, Wu J. The Axin2 rs2240308 polymorphism and susceptibility to lung cancer in a Chinese population. Tumour Biol. 2014;35(11):10987–91.PubMedCrossRef Liu D, Li L, Yang Y, Liu W, Wu J. The Axin2 rs2240308 polymorphism and susceptibility to lung cancer in a Chinese population. Tumour Biol. 2014;35(11):10987–91.PubMedCrossRef
12.
go back to reference Mostowska A, Pawlik P, Sajdak S, Markowska J, Pawalowska M, Lianeri M, et al. An analysis of polymorphisms within the Wnt signaling pathway in relation to ovarian cancer risk in a Polish population. Mol Diag Ther. 2014;18(1):85–91.CrossRef Mostowska A, Pawlik P, Sajdak S, Markowska J, Pawalowska M, Lianeri M, et al. An analysis of polymorphisms within the Wnt signaling pathway in relation to ovarian cancer risk in a Polish population. Mol Diag Ther. 2014;18(1):85–91.CrossRef
13.
go back to reference Pinarbasi E, Gunes EG, Pinarbasi H, Donmez G, Silig Y. AXIN2 polymorphism and its association with prostate cancer in a Turkish population. Med oncol (Northwood, London, England). 2011;28(4):1373–8.CrossRef Pinarbasi E, Gunes EG, Pinarbasi H, Donmez G, Silig Y. AXIN2 polymorphism and its association with prostate cancer in a Turkish population. Med oncol (Northwood, London, England). 2011;28(4):1373–8.CrossRef
14.
go back to reference Gunes EG, Pinarbasi E, Pinarbasi H, Silig Y. Strong association between lung cancer and the AXIN2 polymorphism. Mol Med Rep. 2009;2(6):1029–35.PubMed Gunes EG, Pinarbasi E, Pinarbasi H, Silig Y. Strong association between lung cancer and the AXIN2 polymorphism. Mol Med Rep. 2009;2(6):1029–35.PubMed
15.
go back to reference Ma C, Liu C, Huang P, Kaku H, Chen J, Guo K, et al. Significant association between the Axin2 rs2240308 single nucleotide polymorphism and the incidence of prostate cancer. Oncol Lett. 2014;8(2):789–94.PubMedCentralPubMed Ma C, Liu C, Huang P, Kaku H, Chen J, Guo K, et al. Significant association between the Axin2 rs2240308 single nucleotide polymorphism and the incidence of prostate cancer. Oncol Lett. 2014;8(2):789–94.PubMedCentralPubMed
16.
go back to reference Kanzaki H, Ouchida M, Hanafusa H, Yano M, Suzuki H, Aoe M, et al. Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population. Int J Mol Med. 2006;18(2):279–84.PubMed Kanzaki H, Ouchida M, Hanafusa H, Yano M, Suzuki H, Aoe M, et al. Single nucleotide polymorphism of the AXIN2 gene is preferentially associated with human lung cancer risk in a Japanese population. Int J Mol Med. 2006;18(2):279–84.PubMed
17.
go back to reference Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.PubMedCrossRef Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. Ann Intern Med. 2009;151(4):264–9.PubMedCrossRef
18.
go back to reference Ioannidis JP, Boffetta P, Little J, O’Brien TR, Uitterlinden AG, Vineis P, et al. Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008;37(1):120–32.PubMedCrossRef Ioannidis JP, Boffetta P, Little J, O’Brien TR, Uitterlinden AG, Vineis P, et al. Assessment of cumulative evidence on genetic associations: interim guidelines. Int J Epidemiol. 2008;37(1):120–32.PubMedCrossRef
19.
go back to reference Thakkinstian A, McEvoy M, Minelli C, Gibson P, Hancox B, Duffy D, et al. Systematic review and meta-analysis of the association between β2-adrenoceptor polymorphisms and asthma: a HuGE review. Am J Epidemiol. 2005;162(3):201–11.PubMedCrossRef Thakkinstian A, McEvoy M, Minelli C, Gibson P, Hancox B, Duffy D, et al. Systematic review and meta-analysis of the association between β2-adrenoceptor polymorphisms and asthma: a HuGE review. Am J Epidemiol. 2005;162(3):201–11.PubMedCrossRef
20.
go back to reference Ye X-H, Bu Z-B, Feng J, Peng L, Liao X-B, Zhu X-L, et al. Association between the TP53 polymorphisms and lung cancer risk: a meta-analysis. Mol Biol Rep. 2013;1–13. Ye X-H, Bu Z-B, Feng J, Peng L, Liao X-B, Zhu X-L, et al. Association between the TP53 polymorphisms and lung cancer risk: a meta-analysis. Mol Biol Rep. 2013;1–13.
21.
go back to reference Higgins J, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Stat Med. 2002;21(11):1539–58.PubMedCrossRef Higgins J, Thompson SG. Quantifying heterogeneity in a meta‐analysis. Stat Med. 2002;21(11):1539–58.PubMedCrossRef
23.
go back to reference Liu X, Li S, Lin XJ, Yan KK, Zhao LY, Bao HH, et al. Association between ITGA3, TP53INP2, and AXIN2 gene polymorphism and papillary thyroid carcinoma. J Jilin Univ Med Edition. 2014;40(2):384–8. Liu X, Li S, Lin XJ, Yan KK, Zhao LY, Bao HH, et al. Association between ITGA3, TP53INP2, and AXIN2 gene polymorphism and papillary thyroid carcinoma. J Jilin Univ Med Edition. 2014;40(2):384–8.
24.
go back to reference Webster MT, Rozycka M, Sara E, Davis E, Smalley M, Young N, et al. Sequence variants of the axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Genes Chromosom Cancer. 2000;28(4):443–53.PubMedCrossRef Webster MT, Rozycka M, Sara E, Davis E, Smalley M, Young N, et al. Sequence variants of the axin gene in breast, colon, and other cancers: an analysis of mutations that interfere with GSK3 binding. Genes Chromosom Cancer. 2000;28(4):443–53.PubMedCrossRef
26.
go back to reference Nelson WJ, Nusse R. Convergence of Wnt, ß-catenin, and cadherin pathways. Science (New York, NY). 2004;303(5663):1483–7.CrossRef Nelson WJ, Nusse R. Convergence of Wnt, ß-catenin, and cadherin pathways. Science (New York, NY). 2004;303(5663):1483–7.CrossRef
27.
go back to reference Tseng R-C, Lin R-K, Wen C, Tseng C, Hsu H-S, Hsu W, et al. Epigenetic silencing of AXIN2/betaTrCP and deregulation of p53-mediated control lead to wild-type β-catenin nuclear accumulation in lung tumorigenesis. Oncogene. 2008;27(32):4488–96.PubMedCrossRef Tseng R-C, Lin R-K, Wen C, Tseng C, Hsu H-S, Hsu W, et al. Epigenetic silencing of AXIN2/betaTrCP and deregulation of p53-mediated control lead to wild-type β-catenin nuclear accumulation in lung tumorigenesis. Oncogene. 2008;27(32):4488–96.PubMedCrossRef
28.
go back to reference Furuhashi M, Yagi K, Yamamoto H, Furukawa Y, Shimada S, Nakamura Y, et al. Axin facilitates Smad3 activation in the transforming growth factor β signaling pathway. Mol Cell Biol. 2001;21(15):5132–41.PubMedCentralPubMedCrossRef Furuhashi M, Yagi K, Yamamoto H, Furukawa Y, Shimada S, Nakamura Y, et al. Axin facilitates Smad3 activation in the transforming growth factor β signaling pathway. Mol Cell Biol. 2001;21(15):5132–41.PubMedCentralPubMedCrossRef
29.
go back to reference Ikushima H, Miyazono K. TGF beta signalling: a complex web in cancer progression. Nat Rev Cancer. 2010;10(6):415–24.PubMedCrossRef Ikushima H, Miyazono K. TGF beta signalling: a complex web in cancer progression. Nat Rev Cancer. 2010;10(6):415–24.PubMedCrossRef
30.
go back to reference Yang L-H, Xu H-T, Li Q-C, Jiang G-Y, Zhang X-P, Zhao H-Y, et al. Abnormal hypermethylation and clinicopathological significance of Axin gene in lung cancer. Tumor Biol. 2013;34(2):749–57.CrossRef Yang L-H, Xu H-T, Li Q-C, Jiang G-Y, Zhang X-P, Zhao H-Y, et al. Abnormal hypermethylation and clinicopathological significance of Axin gene in lung cancer. Tumor Biol. 2013;34(2):749–57.CrossRef
31.
go back to reference Kordi Tamandani MK, Sobti RC, Shekari M, Mukesh M, Suri V. Expression and polimorphism of IFN-gamma gene in patients with cervical cancer. Exp Oncol. 2008;30(3):224–9.PubMed Kordi Tamandani MK, Sobti RC, Shekari M, Mukesh M, Suri V. Expression and polimorphism of IFN-gamma gene in patients with cervical cancer. Exp Oncol. 2008;30(3):224–9.PubMed
32.
go back to reference Gangwar R, Pandey S, Mittal RD. Association of interferon-gamma +874A polymorphism with the risk of developing cervical cancer in north-Indian population. BJOG. 2009;116(12):1671–7.PubMedCrossRef Gangwar R, Pandey S, Mittal RD. Association of interferon-gamma +874A polymorphism with the risk of developing cervical cancer in north-Indian population. BJOG. 2009;116(12):1671–7.PubMedCrossRef
33.
go back to reference Lee JE, Lee SJ, Namkoong SE, Um SJ, Sull JW, Jee SH, et al. Gene-gene and gene-environmental interactions of p53, p21, and IRF-1 polymorphisms in Korean women with cervix cancer. Int J Gynecol Cancer. 2004;14(1):118–25.PubMedCrossRef Lee JE, Lee SJ, Namkoong SE, Um SJ, Sull JW, Jee SH, et al. Gene-gene and gene-environmental interactions of p53, p21, and IRF-1 polymorphisms in Korean women with cervix cancer. Int J Gynecol Cancer. 2004;14(1):118–25.PubMedCrossRef
34.
go back to reference Qin X, Peng Q, Chen Z, Deng Y, Huang S, Xu J, et al. The association between MTHFR gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis. PLoS ONE. 2013;8(2), e56070.PubMedCentralPubMedCrossRef Qin X, Peng Q, Chen Z, Deng Y, Huang S, Xu J, et al. The association between MTHFR gene polymorphisms and hepatocellular carcinoma risk: a meta-analysis. PLoS ONE. 2013;8(2), e56070.PubMedCentralPubMedCrossRef
Metadata
Title
AXIN2 rs2240308 polymorphism contributes to increased cancer risk: evidence based on a meta-analysis
Authors
Zhitong Wu
Yifan Sun
Shifu Tang
Chunming Liu
Shengbo Zhu
Lili Wei
Hong Xu
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Cancer Cell International / Issue 1/2015
Electronic ISSN: 1475-2867
DOI
https://doi.org/10.1186/s12935-015-0219-8

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