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Published in: BMC Cancer 1/2016

Open Access 01-12-2016 | Research article

Genetic polymorphism rs3760396 of the chemokine (C-C motif) ligand 2 gene (CCL2) associated with the susceptibility of lung cancer in a pathological subtype-specific manner in Han-ancestry Chinese: a case control study

Authors: Xu Li, Fangcai Lin, Hong Zhou

Published in: BMC Cancer | Issue 1/2016

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Abstract

Background

Chemokines are well known inflammatory factors critical for tumor development in diverse tissues, including lung cancer. Chemokine (C-C motif) Ligand 2 (CCL2) was one of such chemokines important for both primary tumor development and metastasis of various cancers. Polymorphism at rs3760396 of CCL2 genes is associated with the prognosis of non-small cell lung cancer (NSCLC). The goal of our study was to examine the relationship of genetic polymorphisms rs3760396 with the susceptibility of lung cancer and its pathological subtypes in Han-ancestry Chinese population.

Methods

rs3760396 G/C polymorphism of CCL2 was genotyped using PCR in 394 patients with lung cancer and 545 cancer-free controls from the same Northeast region of China.

Results

After controlling for gender, age and smoking status, no significant association was observed between rs3760396 polymorphism and overall lung cancer. However, minor allele G of rs3760396 polymorphism was significantly associated with increased risk of adenosquamous lung carcinoma with either allelic genetic model (OR = 5.29, P < 0.001), or dominant genetic model (OR = 9.88, P < 0.001), or genotypic model (GC genotype vs. CC genotype, OR = 10.73, P < 0.001). Although rs3760396 polymorphism was not significantly associated with increased risk of adenocarcinoma subtype, it was nominally associated with the pooled outcome of either adenocarcinoma or adenosquamous carcinoma under allelic genetic model (OR = 1.54, P = 0.023) or dominant genetic model (OR = 1.57, P = 0.031).

Conclusions

Our study suggested rs3760396 polymorphism of CCL2 is associated not only with prognosis of NSCLC, but also with risk of lung cancer in a subtype-specific manner. Our results further supported previous evidence of the important role of CCL2 in lung cancer development.
Literature
1.
go back to reference Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014;136(5):E359–86.CrossRefPubMed Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D, Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2014;136(5):E359–86.CrossRefPubMed
2.
go back to reference He J, Chen W. National Office for Cancer Prevention and Control, National Center for Cancer Registry, Disease Prevention and Control Bureau, MOH. Beijing: Military Medical Science Press; 2012. He J, Chen W. National Office for Cancer Prevention and Control, National Center for Cancer Registry, Disease Prevention and Control Bureau, MOH. Beijing: Military Medical Science Press; 2012.
3.
go back to reference Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z et al. SEER Cancer Statistics Review, 1975–2011. In: SEER web site. Bethesda, MD: National Cancer Institute; 2014 Howlader N, Noone AM, Krapcho M, Garshell J, Miller D, Altekruse SF, Kosary CL, Yu M, Ruhl J, Tatalovich Z et al. SEER Cancer Statistics Review, 1975–2011. In: SEER web site. Bethesda, MD: National Cancer Institute; 2014
4.
go back to reference Matakidou A, Eisen T, Houlston RS. Systematic review of the relationship between family history and lung cancer risk. Br J Cancer. 2005;93(7):825–33.CrossRefPubMedPubMedCentral Matakidou A, Eisen T, Houlston RS. Systematic review of the relationship between family history and lung cancer risk. Br J Cancer. 2005;93(7):825–33.CrossRefPubMedPubMedCentral
5.
go back to reference Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J. et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet. 2008;40(5):616–22.CrossRefPubMedPubMedCentral Amos CI, Wu X, Broderick P, Gorlov IP, Gu J, Eisen T, Dong Q, Zhang Q, Gu X, Vijayakrishnan J. et al. Genome-wide association scan of tag SNPs identifies a susceptibility locus for lung cancer at 15q25.1. Nat Genet. 2008;40(5):616–22.CrossRefPubMedPubMedCentral
6.
go back to reference Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P. et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008;452(7187):633–7.CrossRefPubMed Hung RJ, McKay JD, Gaborieau V, Boffetta P, Hashibe M, Zaridze D, Mukeria A, Szeszenia-Dabrowska N, Lissowska J, Rudnai P. et al. A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25. Nature. 2008;452(7187):633–7.CrossRefPubMed
7.
go back to reference Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, Qureshi M, Dong Q, Gu X, Chen WV. et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008;40(12):1407–9.CrossRefPubMedPubMedCentral Wang Y, Broderick P, Webb E, Wu X, Vijayakrishnan J, Matakidou A, Qureshi M, Dong Q, Gu X, Chen WV. et al. Common 5p15.33 and 6p21.33 variants influence lung cancer risk. Nat Genet. 2008;40(12):1407–9.CrossRefPubMedPubMedCentral
8.
go back to reference Wu X, Zhao H, Suk R, Christiani DC. Genetic susceptibility to tobacco-related cancer. Oncogene. 2004;23(38):6500–23.CrossRefPubMed Wu X, Zhao H, Suk R, Christiani DC. Genetic susceptibility to tobacco-related cancer. Oncogene. 2004;23(38):6500–23.CrossRefPubMed
9.
go back to reference Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18(26):3831–52.CrossRefPubMed Vendramini-Costa DB, Carvalho JE. Molecular link mechanisms between inflammation and cancer. Curr Pharm Des. 2012;18(26):3831–52.CrossRefPubMed
10.
go back to reference Suzuki M, Mohamed S, Nakajima T, Kubo R, Tian L, Fujiwara T, Suzuki H, Nagato K, Chiyo M, Motohashi S. et al. Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis. Int J Oncol. 2008;33(1):113–9.PubMed Suzuki M, Mohamed S, Nakajima T, Kubo R, Tian L, Fujiwara T, Suzuki H, Nagato K, Chiyo M, Motohashi S. et al. Aberrant methylation of CXCL12 in non-small cell lung cancer is associated with an unfavorable prognosis. Int J Oncol. 2008;33(1):113–9.PubMed
11.
go back to reference Yuan A, Yang PC, Yu CJ, Chen WJ, Lin FY, Kuo SH, Luh KT. Interleukin-8 messenger ribonucleic acid expression correlates with tumor progression, tumor angiogenesis, patient survival, and timing of relapse in non-small-cell lung cancer. Am J Respir Crit Care Med. 2000;162(5):1957–63.CrossRefPubMed Yuan A, Yang PC, Yu CJ, Chen WJ, Lin FY, Kuo SH, Luh KT. Interleukin-8 messenger ribonucleic acid expression correlates with tumor progression, tumor angiogenesis, patient survival, and timing of relapse in non-small-cell lung cancer. Am J Respir Crit Care Med. 2000;162(5):1957–63.CrossRefPubMed
13.
go back to reference Ghilardi G, Biondi ML, La Torre A, Battaglioli L, Scorza R. Breast cancer progression and host polymorphisms in the chemokine system: role of the macrophage chemoattractant protein-1 (MCP-1) -2518 G allele. Clin Chem. 2005;51(2):452–5.CrossRefPubMed Ghilardi G, Biondi ML, La Torre A, Battaglioli L, Scorza R. Breast cancer progression and host polymorphisms in the chemokine system: role of the macrophage chemoattractant protein-1 (MCP-1) -2518 G allele. Clin Chem. 2005;51(2):452–5.CrossRefPubMed
14.
go back to reference Tse KP, Tsang NM, Chen KD, Li HP, Liang Y, Hsueh C, Chang KP, Yu JS, Hao SP, Hsieh LL et al. MCP-1 Promoter Polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment. Clin Cancer Res. 2007;13(21):6320–6.CrossRefPubMed Tse KP, Tsang NM, Chen KD, Li HP, Liang Y, Hsueh C, Chang KP, Yu JS, Hao SP, Hsieh LL et al. MCP-1 Promoter Polymorphism at 2518 is associated with metastasis of nasopharyngeal carcinoma after treatment. Clin Cancer Res. 2007;13(21):6320–6.CrossRefPubMed
15.
go back to reference Ma H, Shu Y, Pan S, Chen J, Dai J, Jin G, Hu Z, Shen H. Polymorphisms of key chemokine genes and survival of non-small cell lung cancer in Chinese. Lung Cancer. 2011;74(2):164–9.CrossRefPubMed Ma H, Shu Y, Pan S, Chen J, Dai J, Jin G, Hu Z, Shen H. Polymorphisms of key chemokine genes and survival of non-small cell lung cancer in Chinese. Lung Cancer. 2011;74(2):164–9.CrossRefPubMed
17.
go back to reference Zeng L, Wang X, Zhou L, Guo C, Cai C, Wu J. Clinicopathological significance of chemotactic factor IL-8, MCP-1 and MIP-1α expressions in gallbladder carcinoma. Chin Ger J Clin Oncol. 2013;12:481–6.CrossRef Zeng L, Wang X, Zhou L, Guo C, Cai C, Wu J. Clinicopathological significance of chemotactic factor IL-8, MCP-1 and MIP-1α expressions in gallbladder carcinoma. Chin Ger J Clin Oncol. 2013;12:481–6.CrossRef
18.
go back to reference Kuroda T, Kitadai Y, Tanaka S, Yang X, Mukaida N, Yoshihara M, Chayama K. Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment. Clin Cancer Res. 2005;11(21):7629–36.CrossRefPubMed Kuroda T, Kitadai Y, Tanaka S, Yang X, Mukaida N, Yoshihara M, Chayama K. Monocyte chemoattractant protein-1 transfection induces angiogenesis and tumorigenesis of gastric carcinoma in nude mice via macrophage recruitment. Clin Cancer Res. 2005;11(21):7629–36.CrossRefPubMed
19.
go back to reference Nakashima E, Mukaida N, Kubota Y, Kuno K, Yasumoto K, Ichimura F, Nakanishi I, Miyasaka M, Matsushima K. Human MCAF gene transfer enhances the metastatic capacity of a mouse cachectic adenocarcinoma cell line in vivo. Pharm Res. 1995;12(11):1598–604.CrossRefPubMed Nakashima E, Mukaida N, Kubota Y, Kuno K, Yasumoto K, Ichimura F, Nakanishi I, Miyasaka M, Matsushima K. Human MCAF gene transfer enhances the metastatic capacity of a mouse cachectic adenocarcinoma cell line in vivo. Pharm Res. 1995;12(11):1598–604.CrossRefPubMed
20.
go back to reference Yang L, Shi GL, Song CX, Xu SF. Relationship between genetic polymorphism of MCP-1 and non-small-cell lung cancer in the Han nationality of North China. Genet Mol Res. 2010;9(2):765–71.CrossRefPubMed Yang L, Shi GL, Song CX, Xu SF. Relationship between genetic polymorphism of MCP-1 and non-small-cell lung cancer in the Han nationality of North China. Genet Mol Res. 2010;9(2):765–71.CrossRefPubMed
21.
go back to reference Wei X, Tian Y, Lu W, Li W, Zhang M, Lu X, Liu Y. Functional polymorphisms in monocyte chemoattractant protein-1 are associated with increased susceptibility to ovarian cancer. DNA Cell Biol. 2015;34(1):37–42.CrossRefPubMed Wei X, Tian Y, Lu W, Li W, Zhang M, Lu X, Liu Y. Functional polymorphisms in monocyte chemoattractant protein-1 are associated with increased susceptibility to ovarian cancer. DNA Cell Biol. 2015;34(1):37–42.CrossRefPubMed
22.
go back to reference Ma J, Wang Q, Fei T, Han JD, Chen YG. MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth muscle cell migration. Blood. 2007;109(3):987–94.CrossRefPubMed Ma J, Wang Q, Fei T, Han JD, Chen YG. MCP-1 mediates TGF-beta-induced angiogenesis by stimulating vascular smooth muscle cell migration. Blood. 2007;109(3):987–94.CrossRefPubMed
23.
go back to reference Nyquist P, Zhang J, De Graba TJ. The −928 G/C and −362 G/C single-nucleotide polymorphisms in the promoter of MCP-1: Increased transcriptional activity and novel binding sites. Cerebrovasc Dis. 2010;29(3):242–7.CrossRefPubMed Nyquist P, Zhang J, De Graba TJ. The −928 G/C and −362 G/C single-nucleotide polymorphisms in the promoter of MCP-1: Increased transcriptional activity and novel binding sites. Cerebrovasc Dis. 2010;29(3):242–7.CrossRefPubMed
Metadata
Title
Genetic polymorphism rs3760396 of the chemokine (C-C motif) ligand 2 gene (CCL2) associated with the susceptibility of lung cancer in a pathological subtype-specific manner in Han-ancestry Chinese: a case control study
Authors
Xu Li
Fangcai Lin
Hong Zhou
Publication date
01-12-2016
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2016
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-016-2328-8

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