MCP-1-2518 A>G and CCR2 V64I polymorphisms in Turkish patients with lung cancer
MCP-1-2518 A>G and CCR2 V64I polymorphisms in Turkish patients with lung cancer
In the current study, we aimed to investigate the possible role of MCP-1 -2518 A>G and CC chemokine receptor 2 (CCR2) V64I polymorphisms in patients with lung cancer. Sixty-five patients with lung cancer (57 with NSCLC and 8 with SCLC) and 57 healthy controls were enrolled. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) method was used. Genotype distribution of monocyte chemoattractant protein 1 (MCP-1) -2518 A>G polymorphism in lung cancer patients was as follows: 30 for AA, 30 for AG and 5 for GG genotype. Frequency of minor G allele in patients and controls were found as 30.8% and 23.7%, respectively. In patients, genotype distribution of CCR2 V64I polymorphism was as follows: 47 for GG, 16 for GA, and 2 for AA. Frequency of minor A allele was found in patients and controls as 15.4% and 19.2%, respectively. Genotype distribution and allele frequencies of MCP-1 and CCR2 polymorphism were not statistically different between patients and controls (p values >0.05 for both polymorphisms). In lung cancer patients, there was no significant association between smoking status and MCP-1 and CCR2 polymorphisms. Similarly, no significant association was found between distant organ metastasis and both gene polymorphisms. Our findings suggest that MCP1 -2518 A>G and CCR2 V64I polymorphisms are not associated with genetic susceptibility to lung cancer and lung cancer metastasis.
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- Arslan, S., Dogan, T., Koksal, B., Yildirim, M.E., Gumus, C., Elagoz, S., Akkurt, I., Ozdemir, O., 2008. Tumoral tissue specific promoter hypermethylation of distinct tumor suppressor genes in a case with nonsmall cell lung carcinoma: A case report. Lung India. 25, 148-151. doi:10.4103/0970-2113.45279.
- Bagci, B., Bagci, G., Candan, F., Ozdemir, O., Sezgin, I., 2015. The protective effect of MCP-1-2518 A> G promoter polymorphism in Turkish chronic renal failure patients requiring long-term hemodialysis. Int. Urol. Nephrol. 47, 551-556. doi:10.1007/ s11255-015-0922-3.
- Balkwill, F., 2003. Chemokine biology in cancer. Semin. Immunol. 5, 49-55. doi:10.1016/S1044-5323(02)00127-6.
- Bektas-Kayhan, K., Unur, M., Boy-Metin, Z., Cakmakoglu, B., 2012. MCP-1 and CCR2 gene variants in oral squamous cell carcinoma. Oral Dis. 18, 55-59. doi:10.1111/j.1601-0825.2011.01843.x.
- Cai, Z., Chen, Q., Chen, J., Lu, Y., Xiao, X., Wu, Z., Zhou, Q., Zhang, J., 2009. Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive lesions in vitro. Neoplasia. 11, 228-236. doi:10.1593/neo.81282.
- Charo, I.F., Taubman, M.B., 2004. Chemokines in the pathogenesis of vascular disease. Circ. Res. 95, 858-866. doi: 10.1161/01. RES.0000146672.10582.17.
- Cruz, C.S.D., Tanoue, L.T., Matthay, R.A., 2011. Lung cancer: Epidemiology, etiology, and prevention. Clin. Chest. Med. 32, 605- 644. doi:10.1016/j.ccm.2011.09.001.
- Decramer, M,. Janssens, W., Miravitlles, M., 2012. Chronic obstructive pulmonary disease. Lancet. 379, 1341-1351. doi:10.1016/ S0140-6736(11)60968-9.
- D'hulst, A.I., Vermaelen, K.Y., Brusselle, G.G., Joos, G.F., Pauwels, R.A., 2005. Time course of cigarette smoke-induced pulmonary inflammation in mice. Eur. Respir. J. 26: 204-213. doi:10.1183/09031936.05.00095204.
- Fenoglio, C., Galimberti, D., Lovati, C., Guidi, I., Gatti, A., Fogliarino, S., Tiriticco, M., Mariani, C., Forloni, G., Pettenati, C., Baron, P., Conti, G., Bresolin, N., Scarpini, E., 2004. MCP-1 in Alzheimer's disease patients: A-2518G polymorphism and serum levels. Neurobiol. Aging. 25, 1169-1173. doi:10.1016/j.neurobiolaging.2003.11.008.
- Hamilton, G., Rath, B., 2015. Smoking, inflammation and small cell lung cancer: Recent developments. Wien. Med. Wochenschr. 165, 379-386. doi:10.1007/s10354-015-0381-6.
- Kakinuma, T., Hwang, S.T., 2006. Chemokines, chemokine receptors, and cancer metastasis. J. Leukoc. Biol. 79, 639-651. doi:10.1189/jlb.1105633.
- Katrancioglu, N., Manduz, S., Karahan, O., Yilmaz, M.B., Sezgin, I., Bagci, G., Berkan, O., 2011. The role of the CCR2 gene polymorphism in abdominal aortic aneurysms. Angiology. 62, 140-143. doi:10.1177/0003319710385335.
- Lee, B., Doranz, B.J., Rana, S., Yi, Y., Mellado, M., Frade, J.M.R., Martinez-A, C., O'Brien, S.J., Dean, M., Collman, R.G., Doms R.V., 1998. Influence of the CCR2-V64I polymorphism on human immunodeficiency virus type 1 coreceptor activity and on chemokine receptor function of CCR2b, CCR3, CCR5, and CXCR4. J. Virol. 72, 7450-7458.
- Lu, X., Kang, Y., 2009. Chemokine (C-C motif) ligand 2 engages CCR2+ stromal cells of monocytic origin to promote breast cancer metastasis to lung and bone. J. Biol. Chem. 284, 29087-29096. doi:10.1074/jbc.M109.035899.
- Mantovani, A., Allavena, P., Sozzani, S., Vecchi, A., Locati, M., Sica, A., 2004. Chemokines in the recruitment and shaping of the leukocyte infiltrate of tumors. Semin. Cancer Biol. 14, 155-160. doi:10.1016/j.semcancer.2003.10.001.
- Molfino, N.A., Jeffery, P.K., 2007. Chronic obstructive pulmonary disease: Histopathology, inflammation and potential therapies. Pulm. Pharmacol. Ther. 2007, 20, 462-472. doi: 10.1016/j.pupt.2006.04.003.
- Narter, K.F., Agachan, B., Sozen, S., Cincin, Z.B., Isbir, T., 2010. CCR2-64I is a risk factor for development of bladder cancer. Genet. Mol. Res. 9, 685-692. doi: 10.4238/vol9-2gmr829.
- Negus, R.P., Stamp, G.W., Hadley, J., Balkwill, F.R., 1997. Quantitative assessment of the leukocyte infiltrate in ovarian cancer and its relationship to the expression of C-C chemokines. Am. J. Pathol. 150, 1723-1734.
- Rafrafi, A., Kaabachi, S., Kaabachi, W., Chahed, B., Amor, A.B., Mbarik, M., Charrad, R., Salah, M.O., Hamzaoui, K., Sassi, F.H., 2015. CCR2-64I polymorphism is associated with non-small cell lung cancer in Tunisian patients. Hum. Immunol. 76, 348- 354. doi:10.1016/j.humimm.2015.03.003.
- Rivas-Fuentes, S., Salgado-Aguayo, A., Belloso, S.P., Rosete, P.G., Alvarado-Vásquez, N., Aquino-Jarquin, G., 2015. Role of Chemokines in non-small cell lung cancer: Angiogenesis and inflammation. J. Cancer. 6, 938-952. doi:10.7150/jca.12286.
- Rose, C.E.Jr., Sung, S.S., Fu, S.M., 2003. Significant involvement of CCL2 (MCP-1) in inflammatory disorders of the lung. Microcirculation. 10, 273-288. doi:10.1038/sj.mn.7800193.
- Rovin, B.H., Lu, L., Saxena, R.A., 1999. Novel polymorphism in the MCP-1 gene regulatory region that influences MCP-1 expression. Biochem. Biophys. Res. Commun. 259, 344-348. doi:10.1006/bbrc.1999.0796.
- Salcedo, R., Ponce, M.L., Young, H.A., Wasserman, K., Ward, J.M., Kleinman, H.K., Oppenheim, J.J., Murphy, W.J., 2000. Human endothelial cells express CCR2 and respond to MCP-1: Direct role of MCP-1 in angiogenesis and tumor progression. Blood. 96, 34-40.
- Sezgin, I., Koksal, B., Bagci, G., Kurtulgan, H.K., Ozdemir, O., 2011. CCR2 polymorphism in chronic renal failure patients that requiring long-term haemodialysis. Intern. Med. 50, 2457-2461. doi: 10.2169/internalmedicine.50.5119.
- Siegel, R., Ma, J., Zou, Z., Jemal, A., 2014. Cancer statistics. CA Cancer J. Clin. 64, 9-29. doi:10.3322/caac.21208.
- Spira, A., Ettinger, D.S., 2004. Multidisciplinary management of lung cancer. N. Eng. J. Med. 350, 379-392. doi:10.1056/ NEJMra035536.
- Tanaka, T., Terada, M., Ariyoshi, K., Morimoto, K., 2010. Monocyte chemoattractant protein-1/CC chemokine ligand 2 enhances apoptotic cell removal by macrophages through Rac1 activation. Biochem. Biophys. Res. Commun. 399, 677-682. doi:10.1016/j. bbrc.2010.07.141.
- Tuder, R.M., Petrache, I., 2012. Pathogenesis of chronic obstructive pulmonary disease. J. Clin. Invest. 122, 2749-2755. doi:10.1172/ JCI60324.
- Vicari, A.P., Caux, C., 2002. Chemokines in cancer. Cytokine Growth factor Rev. 13, 143-154. doi:10.1016/S1359-6101(01)00033- 8.
- Walser, T., Cui, X., Yanagawa, J., Lee, J.M., Heinrich, E., Lee, G., Sharma, S., Dubinett, S.M., 2008. Smoking and lung cancer: The role of inflammation. Proc. Am. Thorac. Soc. 5, 811-815. doi:10.1513/pats.200809-100TH.
- Watanabe, H., Miki, C., Okugawa, Y., Toiyama, Y., Inoue, Y., Kusunoki, M., 2008. Decreased expression of monocyte chemoattractant protein-1 predicts poor prognosis following curative resection of colorectal cancer. Dis Colon Rectum. 51, 1800-1805. doi:10.1007/s10350-008-9380-7.
- Yang, L., Shi, G.L., Song, C.X., Xu, SF., 2010. Relationship between genetic polymorphism of MCP-1 and non-small-cell lung cancer in the Han nationality of North China. Gen. Mol. Res. 9, 765-771. doi:10.4238/vol9-2gmr740.
- Yang, L., Wang, J., Li, F.G., Han, M., Chang, XJ., Wang, Z.T., 2015. Relationship between genetic polymorphisms in MCP-1, CCR- 2, and non-small-cell lung cancer in the Han nationality of Northern China. Genet. Mol. Res. 14, 3745-3752. doi:10.4238/2015.
- Zafiropoulos, A., Crikas, N., Passam, A.M., Spandidos, D.A., 2004. Significant involvement of CCR2-64I and CXCL12-3a in the development of sporadic breast cancer. J. Med. Genet. 41, 59-64. doi:10.1136/jmg.2003.013649.
- Zhang, X.W., Qin, X., Qin, C.Y., Yin, Y.L., Chen, Y., Zhu, H.L., 2013. Expression of monocyte chemoattractant protein-1 and CC chemokine receptor 2 in non-small cell lung cancer and its significance. Cancer Immunol. Immunother. 62, 563-570. doi:10.1007/s00262-012-1361-y.