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Genetic variations in the PRKCG gene and osteosarcoma risk in a Chinese population: a case-control study

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Tumor Biology

Abstract

Osteosarcoma is a common malignant tumor, which exists widely in the bone of children and adolescents. Protein kinase C gamma (PRKCG) gene, which encodes γPKC, plays important roles in tumor promotion, cell proliferation, differentiation, and migration. The objective of the present study was to investigate the relationship between PRKCG polymorphisms and the risk of osteosarcoma. Five tag single nucleotide polymorphisms (SNPs) of PRKCG were retrieved from the HapMap database and genotyped by the method of SNapShot in a hospital-based study containing 388 patients and 388 healthy individuals. Odds ratios (ORs) and their 95 % confidence intervals (CIs) were used to evaluate the association SPSS 20.0 statistical software package was used to analyze statistical data. Our results suggested that the T/C variant of rs454006 located in the intron 3 region of PRKCG gene was significantly associated with an increased risk of osteosarcoma (CC vs. TT, OR = 1.91; 95 % CI 1.29–2.85; P = 0.001; CC vs. TT+TC, OR = 2.14, 95 % CI = 1.48–3.09, P = 0.001; C vs. T, OR = 1.32, 95 % CI = 1.08–1.62, P = 0.008). Similarly, the rs3745406 T/C variant can also elevate the risk of osteosarcoma in the dominant model (OR = 1.45, 95 % CI = 1.08–1.96, P = 0.014), homozygous model (OR = 1.68, 95 % CI = 1.10–2.59, P = 0.002), and allelic model (OR = 1.31, 95 % CI = 1.07–1.61, P = 0.009). However, there were no significant differences in genotypes and allele frequencies of rs2547362 (T>C), rs8103851 (C>G), and rs2242245 (T>C) SNPs between osteosarcoma patients and healthy controls. The results showed that carrier of rs454006*C allele and rs3745406*C might elevate the risk of osteosarcoma. Further studies are needed to validate the coalition between PRKCG gene polymorphisms and risk of osteosarcoma relying on a larger population that included the participants in different ethnicity and hospital.

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References

  1. Gorlick R, Janeway K, Lessnick S, Randall RL, Marina N. Children's Oncology Group's 2013 blueprint for research: bone tumors. Pediatr Blood Cancer. 2013;60:1009–15.

    Article  PubMed  Google Scholar 

  2. Geller DS, Gorlick R. Osteosarcoma: a review of diagnosis, management, and treatment strategies. Clin Adv Hematol Oncol. 2010;8:705–18.

    PubMed  Google Scholar 

  3. Haddox CL, Han G, Anijar L, Binitie O, Letson GD, et al. Osteosarcoma in pediatric patients and young adults: a single institution retrospective review of presentation, therapy, and outcome. Sarcoma. 2014;2014:402509.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wafa H, Grimer RJ. Surgical options and outcomes in bone sarcoma. Expert Rev Anticancer Ther. 2006;6:239–48.

    Article  PubMed  Google Scholar 

  5. Goricar K, Kovac V, Jazbec J, Zakotnik B, Lamovec J, et al. Influence of the folate pathway and transporter polymorphisms on methotrexate treatment outcome in osteosarcoma. Pharmacogenet Genomics. 2014;24:514–21.

    Article  CAS  PubMed  Google Scholar 

  6. Wittig JC, Bickels J, Priebat D, Jelinek J, Kellar-Graney K, et al. Osteosarcoma: a multidisciplinary approach to diagnosis and treatment. Am Fam Physician. 2002;65:1123–32.

    PubMed  Google Scholar 

  7. Kager L, Zoubek A, Potschger U, Kastner U, Flege S, et al. Primary metastatic osteosarcoma: presentation and outcome of patients treated on neoadjuvant Cooperative Osteosarcoma Study Group protocols. J Clin Oncol. 2003;21:2011–8.

    Article  PubMed  Google Scholar 

  8. Yang LM, Li XH, Bao CF. Glutathione S-transferase P1 and DNA polymorphisms influence response to chemotherapy and prognosis of bone tumors. Asian Pac J Cancer Prev. 2012;13:5883–6.

    Article  PubMed  Google Scholar 

  9. Bai SB, Chen HX, Bao YX, Luo X, Zhong JJ. Predictive impact of common variations in DNA repair genes on clinical outcome of osteosarcoma. Asian Pac J Cancer Prev. 2013;14:3677–80.

    Article  PubMed  Google Scholar 

  10. Teng JW, Yang ZM, Li J, Xu B. Predictive role of glutathione S-transferases (GSTs) on the prognosis of osteosarcoma patients treated with chemotherapy. Pak J Med Sci. 2013;29:1182–6.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Nishizuka Y. Intracellular signaling by hydrolysis of phospholipids and activation of protein kinase C. Science. 1992;258:607–14.

    Article  CAS  PubMed  Google Scholar 

  12. Kofler K, Erdel M, Utermann G, Baier G. Molecular genetics and structural genomics of the human protein kinase C gene module. Genome Biol. 2002;3: RESEARCH0014.

  13. Hawkins MM, Wilson LM, Burton HS, Potok MH, Winter DL, et al. Radiotherapy, alkylating agents, and risk of bone cancer after childhood cancer. J Natl Cancer Inst. 1996;88:270–8.

    Article  CAS  PubMed  Google Scholar 

  14. Zhong GQ, Tu RH, Zeng ZY, Li QJ, He Y, et al. Novel functional role of heat shock protein 90 in protein kinase C-mediated ischemic postconditioning. J Surg Res. 2014;189:198–206.

    Article  CAS  PubMed  Google Scholar 

  15. Chen DH, Brkanac Z, Verlinde CL, Tan XJ, Bylenok L, et al. Missense mutations in the regulatory domain of PKC gamma: a new mechanism for dominant nonepisodic cerebellar ataxia. Am J Hum Genet. 2003;72:839–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Schlaepfer IR, Clegg HV, Corley RP, Crowley TJ, Hewitt JK, et al. The human protein kinase C gamma gene (PRKCG) as a susceptibility locus for behavioral disinhibition. Addict Biol. 2007;12:200–9.

    Article  PubMed  Google Scholar 

  17. Klebe S, Durr A, Rentschler A, Hahn-Barma V, Abele M, et al. New mutations in protein kinase Cgamma associated with spinocerebellar ataxia type 14. Ann Neurol. 2005;58:720–9.

    Article  CAS  PubMed  Google Scholar 

  18. Xu Y, Lopes C, Wende H, Guo Z, Cheng L, et al. Ontogeny of excitatory spinal neurons processing distinct somatic sensory modalities. J Neurosci. 2013;33:14738–48.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Parsons M, Adams JC. Rac regulates the interaction of fascin with protein kinase C in cell migration. J Cell Sci. 2008;121:2805–13.

    Article  CAS  PubMed  Google Scholar 

  20. Mochizuki H, Seki T, Adachi N, Saito N, Mishima HK, et al. R659S mutation of gammaPKC is susceptible to cell death: implication of this mutation/polymorphism in the pathogenesis of retinitis pigmentosa. Neurochem Int. 2006;49:669–75.

    Article  CAS  PubMed  Google Scholar 

  21. Boerman I, Selvarajah GT, Nielen M, Kirpensteijn J. Prognostic factors in canine appendicular osteosarcoma - a meta-analysis. BMC Vet Res. 2012;8:56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Jones KB, Salah Z, Del Mare S, Galasso M, Gaudio E, et al. miRNA signatures associate with pathogenesis and progression of osteosarcoma. Cancer Res. 2012;72:1865–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Ogawa K, Seki T, Onji T, Adachi N, Tanaka S, et al. Mutant gammaPKC that causes spinocerebellar ataxia type 14 upregulates Hsp70, which protects cells from the mutant's cytotoxicity. Biochem Biophys Res Commun. 2013;440:25–30.

    Article  CAS  PubMed  Google Scholar 

  24. Wang X, Sun Y, Sun N, Liu W, Lang XE, et al. Association study between protein kinase C gamma gene polymorphism and major depressive disorder. Zhonghua Yi Xue Za Zhi. 2010;90:738–42.

    CAS  PubMed  Google Scholar 

  25. Newton AC. Protein kinase C: structural and spatial regulation by phosphorylation, cofactors, and macromolecular interactions. Chem Rev. 2001;101:2353–64.

    Article  CAS  PubMed  Google Scholar 

  26. Barmack NH, Qian Z, Yoshimura J. Regional and cellular distribution of protein kinase C in rat cerebellar Purkinje cells. J Comp Neurol. 2000;427:235–54.

    Article  CAS  PubMed  Google Scholar 

  27. Hiramoto K, Kawakami H, Inoue K, Seki T, Maruyama H, et al. Identification of a new family of spinocerebellar ataxia type 14 in the Japanese spinocerebellar ataxia population by the screening of PRKCG exon 4. Mov Disord. 2006;21:1355–60.

    Article  PubMed  Google Scholar 

  28. Vignjevic D, Schoumacher M, Gavert N, Janssen KP, Jih G, et al. Fascin, a novel target of beta-catenin-TCF signaling, is expressed at the invasive front of human colon cancer. Cancer Res. 2007;67:6844–53.

    Article  CAS  PubMed  Google Scholar 

  29. Mazzoni E, Adam A, de Kier B, Joffe E, Aguirre-Ghiso JA. Immortalized mammary epithelial cells overexpressing protein kinase C gamma acquire a malignant phenotype and become tumorigenic in vivo. Mol Cancer Res. 2003;1:776–87.

    CAS  PubMed  Google Scholar 

  30. Griner EM, Kazanietz MG. Protein kinase C and other diacylglycerol effectors in cancer. Nat Rev Cancer. 2007;7:281–94.

    Article  CAS  PubMed  Google Scholar 

  31. Buchet-Poyau K, Mehenni H, Radhakrishna U, Antonarakis SE. Search for the second Peutz-Jeghers syndrome locus: exclusion of the STK13, PRKCG, KLK10, and PSCD2 genes on chromosome 19 and the STK11IP gene on chromosome 2. Cytogenet Genome Res. 2002;97:171–8.

    Article  CAS  PubMed  Google Scholar 

  32. Zheng Q, Du J, Zhang Z, Xu J, Fu L, et al. Association study between of Tie2/angiopoietin-2 and VEGF/KDR pathway gene polymorphisms and vascular malformations. Gene. 2013;523:195–8.

    Article  CAS  PubMed  Google Scholar 

  33. Zhang Y, Hu X, Wang HK, Shen WW, Liao TQ, et al. Single-nucleotide polymorphisms of the PRKCG gene and osteosarcoma susceptibility. Tumour Biol. 2014;35:12671–7.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81272040), the Natural Science Foundation of Guangdong Province, P. R. China (No. S2011010004808, S2013010016385), and the Science and Technology Projects of Guangdong Province, P. R. China (No. 2012B031800451, 2009B06070045).

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Correspondence to Huading Lu.

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Huading Lu and Lei Zhu contributed equally to this work.

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Lu, H., Zhu, L., Lian, L. et al. Genetic variations in the PRKCG gene and osteosarcoma risk in a Chinese population: a case-control study. Tumor Biol. 36, 5241–5247 (2015). https://doi.org/10.1007/s13277-015-3182-z

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  • DOI: https://doi.org/10.1007/s13277-015-3182-z

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