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CD86 gene variants and susceptibility to pancreatic cancer

  • Original Paper
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Abstract

Background

Pancreatic cancer is one of the most lethal cancers worldwide. CD86 (B7-2) is a costimulatory molecule on antigen-presenting cells and plays critical roles in tumor immunity. It has been reported that polymorphisms in CD86 gene can be involved in the development of various cancers. Here, we investigated the association of two CD86 polymorphisms, +1057G/A (rs1129055) and +2379G/C (rs17281995), with pancreatic cancer in the Chinese population.

Methods

The two polymorphisms were identified in 369 pancreatic cancer patients and 412 healthy controls using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP). Data were analyzed by chi-square test and adjusted for body mass index, smoking, drinking, and diabetes status.

Results

Results showed that the frequency of the +1057A allele was significantly higher in pancreatic cancer cases than in controls (59.8 vs. 52.8 %, p = 0.021). Comparison of genotype frequencies showed that +1057GA and +1057AA genotypes were significantly increased in the pancreatic cancer group (odds ratio (OR) = 1.52; 95 % confidence interval (CI), 1.09–2.38; p = 0.026; and OR = 1.90; 95 % CI, 1.21–3.01; p = 0.007). We did not find any association between the +2379G/C polymorphism and pancreatic cancer. Analysis of haplotypes indicated that the AG (+1057, +2379) haplotype was correlated with the susceptibility to this disease (p = 0.019).

Conclusions

These results suggest that the CD86 +1057G/A polymorphism and AG (+1057, +2379) haplotype are genetic risk factors for pancreatic cancer.

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References

  • Allison JP, Hurwitz AA, Leach DR (1995) Manipulation of costimulatorysignals to enhance antitumor T-cell responses. Curr Opin Immunol 7(5):682–686

    Article  CAS  PubMed  Google Scholar 

  • Amundadottir L, Kraft P, Stolzenberg-Solomon RZ, Fuchs CS, Petersen GM, Arslan AA (2009) Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer. Nat Genet 41(9):986–990

    Article  CAS  PubMed  Google Scholar 

  • Corydon TJ, Haagerup A, Jensen TG, Binderup HG, Petersen MS, Kaltoft K, Vestbo J, Kruse TA, Borglum AD (2007) A functional CD86 polymorphism associated with asthma and related allergic disorders. J Med Genet 44(8):509–515

    Article  CAS  PubMed  Google Scholar 

  • Delneste Y, Bosotti R, Magistrelli G, Bonnefoy JY, Gauchat JF (2000) Detection of a polymorphism in exon 8 of the human CD86 gene. Immunogenetics 51(8–9):762–763

    Article  CAS  PubMed  Google Scholar 

  • Evans DB, Lee JE, Pisters PW, Charnsangavej C, Ellis LM, Chiao PJ, Lenzi R, Abbruzzese JL (1997) Advances in the diagnosis and treatment of adenocarcinoma of the pancreas. Cancer Treat Res 90:109–125

    Article  CAS  PubMed  Google Scholar 

  • Greenwald RJ, Freeman GJ, Sharpe AH (2005) The B7 family revisited. Annu Rev Immunol 23:515–548

    Article  PubMed  Google Scholar 

  • Hodge JW, Abrams S, Schlom J, Kantor JA (1994) Induction of antitumor immunity by recombinant vaccinia viruses expressing B7-1 or B7-2 costimulatory molecules. Cancer Res 54(21):5552–5555

    CAS  PubMed  Google Scholar 

  • Jellis CL, Wang SS, Rennert P, Borriello F, Sharpe AH, Green NR, Gray GS (1995) Genomic organization of the gene coding for the costimulatory human B-lymphocyte antigen B7-2 (CD86). Immunogenetics 42(2):85–89

    Article  CAS  PubMed  Google Scholar 

  • Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ (2007) Cancer statistics. CA Cancer J Clin 57(1):43–66

    Article  PubMed  Google Scholar 

  • Kronfeld K, Abken H, Seliger B (2005) B7-1 and B7-2 act differentially in the induction of a T cell response: their impact for a HLA-matched and HLA-mismatched anti-tumor immunotherapy. Int J Cancer 117(5):794–799

    Article  CAS  PubMed  Google Scholar 

  • Krummel MF, Allison JP (1995) CD28 and CTLA-4 have opposing effects on the response of T cells to stimulation. J Exp Med 182(2):459–465

    Article  CAS  PubMed  Google Scholar 

  • Landi D, Moreno V, Guino E, Vodicka P, Pardini B, Naccarati A, Canzian F, Barale R, Gemignani F, Landi S (2011) Polymorphisms affecting micro-RNA regulation and associated with the risk of dietary-related cancers: a review from the literature and new evidence for a functional role of rs17281995 (CD86) and rs1051690 (INSR), previously associated with colorectal cancer. Mutat Res 717(1–2):109–115

    CAS  PubMed  Google Scholar 

  • Lang C, Chen L, Li S (2011) Cytotoxic T-lymphocyte antigen-4 +49G/A polymorphism and susceptibility to pancreatic cancer. DNA Cell Biol 31(5):683–687

    Article  PubMed  Google Scholar 

  • Loos M, Giese NA, Kleeff J, Giese T, Gaida MM, Bergmann F, Laschinger M, Büchler M, Friess H (2008) Clinical significance and regulation of the costimulatory molecule B7–H1 in pancreatic cancer. Cancer Lett 268(1):98–109

    Article  CAS  PubMed  Google Scholar 

  • Loser K, Scherer A, Krummen MB, Varga G, Higuchi T, Schwarz T, Sharpe AH, Grabbe S, Bluestone JA, Beissert S (2005) An important role of CD80/CD86-CTLA-4 signaling during photocarcinogenesis in mice. J Immunol 174(9):5298–5305

    Google Scholar 

  • Marin LA, Moya-Quiles MR, Miras M, Muro M, Minguela A, Bermejo J, Ramirez P, Garcia-Alonso AM, Parrilla P, Alvarez-Lopez MR (2005) Evaluation of CD86 gene polymorphism at +1057 position in liver transplant recipients. Transpl Immunol 15(1):69–74

    Article  CAS  PubMed  Google Scholar 

  • Nunes JA, Truneh A, Olive D, Cantrell DA (1996) Signal transduction by CD28 costimulatory receptor on T cells B7-1 and B7-2 regulation of tyrosine kinase adaptor molecules. J Biol Chem 271(3):1591–1598

    Article  CAS  PubMed  Google Scholar 

  • Pan XM, Gao LB, Liang WB, Liu Y, Zhu Y, Tang M, Li YB, Zhang L (2010) CD86 +1057G/A polymorphism and the risk of colorectal cancer. DNA Cell Biol 29(7):381–386

    Article  CAS  PubMed  Google Scholar 

  • Petersen GM, Amundadottir L, Fuchs CS, Kraft P, Stolzenberg- Solomon RZ, Jacobs KB et al (2010) A genome-wide association study identifies pancreatic cancer susceptibility loci on chromosomes 13q22.1, 1q32.1, 5p15.33. Nat Genet 42(3):224–228

    Article  CAS  PubMed  Google Scholar 

  • Pizzoferrato E (2004) B7-2 expression above a threshold elicits anti-tumor immunity as effective as interleukin-12 and prolongs survival in murine B-cell lymphoma. Int J Cancer 110(1):61–69

    Article  CAS  PubMed  Google Scholar 

  • Roitt I, Brostoff J, Male D (2001) Immunology, 6th edn. Mosby, London

    Google Scholar 

  • Royal RE, Levy C, Turner K, Mathur A, Hughes M, Kammula US, Sherry RM, Topalian SL, Yang JC, Lowy I, Rosenberg SA (2010) Phase 2 trial of single agent Ipilimumab (anti-CTLA-4) for locally advanced or metastatic pancreatic adenocarcinoma. J Immunother 33(8):828–833

    Article  CAS  PubMed  Google Scholar 

  • Salomon B, Bluestone JA (2001) Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 19:225–252

    Article  CAS  PubMed  Google Scholar 

  • Seliger B, Marincola FM, Ferrone S, Abken H (2008) The complex role of B7 molecules in tumor immunology. Trends Mol Med 14(12):550–559

    Article  CAS  PubMed  Google Scholar 

  • Shi YY, He L (2005) SHEsis, a powerful software platform for analyses of linkage disequilibrium, haplotype construction, and genetic association at polymorphism loci. Cell Res 15(2):97–98

    Article  CAS  PubMed  Google Scholar 

  • Slavik JM, Hutchcroft JE, Bierer BE (1999) CD80 and CD86 are not equivalent in their ability to induce the tyrosine phosphorylation of CD28. J Biol Chem 274(5):3116–3124

    Article  CAS  PubMed  Google Scholar 

  • Stremmel C, Greenfield EA, Howard E, Freeman GJ, Kuchroo VK (1999) B7-2 expressed on EL4 lymphoma CD86 +1057G/A polymorphism and cancer 385 suppresses antitumor immunity by an interleukin 4-dependent mechanism. J Exp Med 189(6):919–930

    Article  CAS  PubMed  Google Scholar 

  • Ueda Y, Levine BL, Huang ML, Freeman GJ, Nadler LM, June CH, Ward SG (1995) Both CD28 ligands CD80 (B7-1) and CD86 (B7-2) activate phosphatidylinositol 3-kinase, and wortmannin reveals heterogeneity in the regulation of T cell IL-2 secretion. Int Immunol 7(6):957–966

    Article  CAS  PubMed  Google Scholar 

  • Waterhouse P, Penninger JM, Timms E, Wakeham A, Shahinian A, Lee KP, Thompson CB, Griesser H, Mak TW (1995) Lymphoproliferative disorders with early lethality in mice deficient in Ctla-4. Science 270(5238):985–988

    Article  CAS  PubMed  Google Scholar 

  • Yang M, Sun T, Zhou Y, Wang L, Liu L, Zhang X, Tang X, Zhou M, Kuang P, Tan W, Li H, Yuan Q, Yu D (2012) The functional cytotoxic T lymphocyte-associated Protein 4 49G-to-A genetic variant and risk of pancreatic cancer. Cancer. doi:101002/cncr27455

    Google Scholar 

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No competing financial interests exist.

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Authors and Affiliations

  1. Department of General Surgery, Shanghai Changzheng Hospital, Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China

    Honggang Xiang, Yanping Sun, Jun Yao, Jian Xu, Yi Wang, Houshan Yao & Zhiqian Hu

  2. Department of Hepatobiliary Surgery, Second Artillery General Hospital, Beijing, 100088, China

    Wei Zhao

  3. Neuroscience Program, University of Toronto, Toronto, ON, M1C 1A4, Canada

    Winnie Qian

  4. Department of General Surgery, Shanghai Changhai Hospital, Second Military Medical University, Shanghai, 200433, China

    Junjie Xing

  5. School of Occupational Therapy, University of Western Ontario, London, ON, N6G 1H1, Canada

    Yujia Zhou

Authors
  1. Honggang Xiang
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  2. Wei Zhao
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  3. Yanping Sun
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  4. Winnie Qian
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  5. Junjie Xing
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  7. Jun Yao
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  8. Jian Xu
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  9. Yi Wang
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  10. Houshan Yao
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  11. Zhiqian Hu
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Corresponding author

Correspondence to Zhiqian Hu.

Additional information

H. Xiang and W. Zhao contributed equally to this work.

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Xiang, H., Zhao, W., Sun, Y. et al. CD86 gene variants and susceptibility to pancreatic cancer. J Cancer Res Clin Oncol 138, 2061–2067 (2012). https://doi.org/10.1007/s00432-012-1289-9

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  • DOI: https://doi.org/10.1007/s00432-012-1289-9

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