Abstract
CD27 and its ligand, CD70, are major costimulatory molecules whose interaction can regulate the expansion and differentiation of effector and memory T-cell populations. Their abnormal expression can disturb the immune response and lead to an increased risk of cancer. This study aims to evaluate the associations between single nucleotide polymorphisms (SNPs) in CD27/CD70 gene and breast cancer susceptibility. Five tagSNPs and one coding polymorphism in CD27, as well as three tagSNPs in CD70, were genotyped in a case–control study of 610 breast cancer patients and 617 healthy controls. In CD27, rs3136550 CT and rs2267966 AT genotypes were associated with a decreased risk of breast cancer (P = 0.03, OR = 0.76; P = 0.02, OR = 0.75, respectively). In CD70, AG and GG genotypes in rs1862511 and CC genotype in rs2059154 also showed significant associations with a decreased risk of breast cancer (P = 2.00 × 10−3, OR = 0.69; P = 0.03, OR = 0.62; P = 2.00 × 10−3, OR = 0.53; respectively). Significant associations were also found in the dominant and recessive models for rs2059154 and dominant model for rs1862511. In haplotype analysis, CCGAG haplotype in CD27 and TAA haplotype in CD70 conferred an increased risk of breast cancer (P = 5.60 × 10−3; P = 7.75 × 10−5, respectively), but TGC, TAC and TGA haplotypes in CD70 were associated with a decreased risk of breast cancer (P = 0.01; P = 5.2 × 10−3; P = 2.00 × 10−3, respectively). The associations of CCGAG, TAA, TAC and TGA haplotypes remained significant after correcting P value for multiple testing. Significant associations were shown between the SNPs of CD27 and lymph node metastasis, and ER and PR statuses. These results indicate that CD27 and CD70 gene polymorphisms may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in a northern Chinese population.
Similar content being viewed by others
Abbreviations
- CI:
-
Confidence interval
- ER:
-
Estrogen receptor
- Her-2:
-
Human epidermal growth factor receptor 2
- HWE:
-
Hardy–Weinberg equilibrium
- IDC:
-
Infiltrating duct carcinoma
- LD:
-
Linkage disequilibrium
- LN:
-
Lymph node
- OR:
-
Odds ratio
- PCR-RFLP:
-
Polymerase chain reaction-restriction fragment length polymorphism
- PR:
-
Progesterone receptor
- SNPs:
-
Single nucleotide polymorphisms
- TZ:
-
Tumor size
References
Easton DF, Pooley KA, Dunning AM, Pharoah PD, Thompson D, Ballinger DG, Struewing JP, Morrison J, Field H, Luben R et al (2007) Genome-wide association study identifies novel breast cancer susceptibility loci. Nature 447(7148):1087–1093
DeNardo DG, Coussens LM (2007) Inflammation and breast cancer. Balancing immune response: crosstalk between adaptive and innate immune cells during breast cancer progression. Breast Cancer Res 9(4):212
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer immunoediting: from immunosurveillance to tumor escape. Nat Immunol 3:991–998
Disis ML, Park KH (2009) Immunomodulation of breast cancer via tumor antigen specific Th1. Cancer Res Treat 41(3):117–121
Whiteside TL (2010) Immune responses to malignancies. J Allergy Clin Immunol 125:S272–S283
Inman BA, Frigola X, Dong H, Kwon ED (2007) Costimulation, coinhibition and cancer. Curr Cancer Drug Target 7(1):15–30
Ghaderi A, Yeganeh F, Kalantari T, Talei AR, Pezeshki AM, Doroudchi M, Dehaghani AS (2004) Cytotoxic T lymphocyte antigen-4 gene in breast cancer. Breast Cancer Res Treat 86(1):1–7
Hua Z, Li D, Xiang G, Xu F, Jie G, Fu Z, Jie Z, Da P, Li D (2011) PD-1 polymorphisms are associated with sporadic breast cancer in Chinese Han population of Northeast China. Breast Cancer Res Treat 129(1):195–201
Akiba H, Nakano H, Nishinaka S, Shindo M, Kobata T, Atsuta M, Morimoto C, Ware CF, Malinin NL, Wallach D et al (1998) CD27, a member of the tumor necrosis factor receptor superfamily, activates NF-kappaB and stress-activated protein kinase/c-Jun N-terminal kinase via TRAF2, TRAF5, and NF-kappaB-inducing kinase. J Biol Chem 273(21):13353–13358
Gravestein LA, Amsen D, Boes M, Calvo CR, Kruisbeek AM, Borst J (1998) The TNF receptor family member CD27 signals to Jun N-terminal kinase via Traf-2. Eur J Immunol 28(7):2208–2216
Lens SM, Tesselaar K, van Oers MH, van Lier RA (1998) Control of lymphocyte function through CD27–CD70 interactions. Semin Immunol 10(6):491–499
Takeda K, Oshima H, Hayakawa Y, Akiba H, Atsuta M, Kobata T, Kobayashi K, Ito M, Yagita H, Okumura K (2000) CD27-mediated activation of murine NK cells. J Immunol 164(4):1741–1745
Arens R, Tesselaar K, Baars PA, van Schijndel GM, Hendriks J, Pals ST, Krimpenfort P, Borst J, van Oers MH, van Lier RA (2001) Constitutive CD27/CD70 interaction induces expansion of effector-type T cells and results in IFN gamma-mediated B cell depletion. Immunity 15(5):801–812
Keller AM, Schildknecht A, Xiao Y, van den Broek M, Borst J (2008) Expression of costimulatory ligand CD70 on steady-state dendritic cells breaks CD8+ T cell tolerance and permits effective immunity. Immunity 29(6):934–946
Arens R, Schepers K, Nolte MA, van Oosterwijk MF, van Lier RA, Schumacher TN, van Oers MH (2004) Tumor rejection induced by CD70-mediated quantitative and qualitative effects on effector CD8+ T cell formation. J Exp Med 199(11):1595–1605
Laouar A, Haridas V, Vargas D, Zhinan X, Chaplin D, van Lier RA, Manjunath N (2005) CD70+ antigen-presenting cells control the proliferation and differentiation of T cells in the intestinal mucosa. Nat Immunol 6(7):698–706
Peperzak V, Xiao Y, Veraar EA, Borst J (2010) CD27 sustains survival of CTLs in virus-infected nonlymphoid tissue in mice by inducing autocrine IL-2 production. J Clin Invest 120(1):168–178
Kelly JM, Darcy PK, Markby JL, Godfrey DI, Takeda K, Yagita H, Smyth MJ (2002) Induction of tumor-specific T cell memory by NK cell-mediated tumor rejection. Nat Immunol 3(1):83–90
Nieland JD, Graus YF, Dortmans YE, Kremers BL, Kruisbeek AM (1998) CD40 and CD70 co-stimulate a potent in vivo antitumor T cell response. J Immunother 21(3):225–236
Yu SE, Park SH, Jang YK (2010) Epigenetic silencing of TNFSF7 (CD70) by DNA methylation during progression to breast cancer. Mol Cells 29(2):217–221
Rahimifar S, Erfani N, Sarraf Z, Ghaderi A (2010) ctla-4 gene variations may influence cervical cancer susceptibility. Gynecol Oncol 119(1):136–139
Cheng TY, Lin JT, Chen LT, Shun CT, Wang HP, Lin MT, Wang TE, Cheng AL, Wu MS (2006) Association of T-cell regulatory gene polymorphisms with susceptibility to gastric mucosa-associated lymphoid tissue lymphoma susceptibility. J Clin Oncol 24(21):3483–3489
Suwalska K, Pawlak E, Karabon L, Tomkiewicz A, Dobosz T, Urbaniak-Kujda D, Kuliczkowski K, Wolowiec D, Jedynak A, Frydecka I (2008) Association studies of CTLA-4, CD28, and ICOS gene polymorphisms with B-cell chronic lymphocytic leukemia in the Polish population. Hum Immunol 69(3):193–201
Hendriks J, Gravestein LA, Tesselaar K, van Lier RA, Schumacher TN, Borst J (2000) CD27 is required for generation and long-term maintenance of T cell immunity. Nat Immunol 5:433–440
Orengo AM, Cantoni C, Neglia F, Biassoni R, Ferrini S (1997) Reciprocal expression of CD70 and of its receptor, CD27, in human long term-activated T and natural killer (NK) cells: inverse regulation by cytokines and role in induction of cytotoxicity. Clin Exp Immunol 107(3):608–613
Balvay L, Libri D, Fiszman MY (1993) Pre-mRNA secondary structure and the regulation of splicing. Bioessays 15(3):165–169
Majewski J, Ott J (2002) Distribution and characterization of regulatory elements in the human genome. Genome Res 12(12):1827–1836
Baralle D, Baralle M (2005) Splicing in action: assessing disease causing sequence changes. J Med Genet 42(10):737–748
Borst J, Hendriks J, Xiao Y (2005) CD27 and CD70 in T cell and B cell activation. Curr Opin Immunol 17(3):275–281
Cormary C, Gonzalez R, Faye JC, Favre G, Tilkin-Mariame AF (2004) Induction of T-cell antitumor immunity and protection against tumor growth by secretion of soluble human CD70 molecules. Cancer Gene Ther 11(7):497–507
Capon F, Allen MH, Ameen M, Burden AD, Tillman D, Barker JN, Trembath RC (2004) A synonymous SNP of the corneodesmosin gene leads to increased mRNA stability and demonstrates association with psoriasis across diverse ethnic groups. Hum Mol Genet 13(20):2361–2368
Nackley AG, Shabalina SA, Tchivileva IE, Satterfield K, Korchynskyi O, Makarov SS, Maixner W, Diatchenko L (2006) Human catechol-O-methyltransferase haplotypes modulate protein expression by altering mRNA secondary structure. Science 314(5807):1930–1933
Nielsen KB, Sorensen S, Cartegni L, Corydon TJ, Doktor TK, Schroeder LD, Reinert LS, Elpeleg O, Krainer AR, Gregersen N et al (2007) Seemingly neutral polymorphic variants may confer immunity to splicing-inactivating mutations: a synonymous SNP in exon 5 of MCAD protects from deleterious mutations in a flanking exonic splicing enhancer. Am J Hum Genet 80(3):416–432
Acknowledgments
Fengyan Xu and Dalin Li designed the primers and wrote the drafts. Dalin Li collected the patient and control blood samples. Fengyan Xu, Qiujin Zhang and Zhenkun Fu performed the PCR-RFLP experiments. Fengyan Xu and Weiguang Yuan contributed to the statistical analysis. Da Pang and Dianjun Li conceived the study and participated in its design and coordination and helped draft the manuscript. All authors read and approved the final manuscript. This study was supported by a grant from the National Natural Science Foundation of China (31070780) and the Major Project of Technology Department, Heilongjiang Province (GB05C402). We thank all patients and healthy volunteers for providing blood samples. We are grateful for the collaboration received from the participating hospitals and their staff.
Conflicts of interests
The authors declare that they have no conflicts of interest.
Author information
Authors and Affiliations
Corresponding authors
Additional information
F. Xu and D. Li authors have contributed equally to this work.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Xu, F., Li, D., Zhang, Q. et al. Association of CD27 and CD70 gene polymorphisms with risk of sporadic breast cancer in Chinese women in Heilongjiang Province. Breast Cancer Res Treat 133, 1105–1113 (2012). https://doi.org/10.1007/s10549-012-1987-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10549-012-1987-7