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Association of BTLA gene polymorphisms with the risk of malignant breast cancer in Chinese women of Heilongjiang Province

  • Epidemiology
  • Published:
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Abstract

B and T lymphocyte attenuator (BTLA) is an immunoinhibitory receptor with the ability to deliver inhibitory signals for suppressing lymphocyte activation. To identify the influences of BTLA gene polymorphisms on the risk of sporadic breast cancer, a case–control study was conducted in women from northeast of China, Heilongjiang Province. We genotyped five SNPs (rs9288952, rs2931761, rs2633562, rs2705535 and rs1844089) in BTLA gene among exons and introns. Our research groups consist of 592 patients with breast cancer and 506 age/sex-matched healthy controls. Genotypes were determined by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and polymerase chain reaction with confronting two-pair primer (PCR-CTPP) methods. Data were analyzed using the chi-square test by EXCEL, SPSS and Haploview softwares. The frequencies of BTLA rs1844089 CT and rs2705535 AG were higher in patients than in controls (P = 0.0164; P = 0.0031), and rs1844089 CC, rs2705535 GG and rs9288952 CC genotypes had lower incidences in patients than in controls (P = 0.0483; P = 0.0098; P = 0.0400). The frequency of haplotype CAAAT was significantly higher in patients (P = 0.0112). Strong association was shown between five SNPs of BTLA gene and tumor size, estrogen receptor (ER), progesterone receptor (PR), C-erbB-2 and P53 statuses. Strong association was observed between tumor size, ER, PR, P53 and the CAGAT(P = 0.012), TAAGT(P = 0.0378), CAGAT(P = 0.0013), CAAGT(P = 0.0373) and CAAAT(P = 0.0306) haplotypes. These results primarily suggested that BTLA gene polymorphisms may affect the sporadic breast cancer risk and prognosis in Chinese women in northeast of Heilongjiang Province.

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Abbreviations

BTLA:

B and T lymphocyte attenuator

CI:

Confidence interval

ER:

Estrogen receptor

HWE:

Hardy–Weinberg equilibrium

LN:

Lymph node

OR:

Odds ratio

PCR-RFLP:

Polymerase chain reaction-restriction fragment length polymorphism

PCR-CTPP:

Polymerase chain reaction with confronting two-pair primer

PR:

Progesterone receptor

SNP:

Single nucleotide polymorphism

TZ:

Tumor size

References

  1. Chen L (2004) Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat Rev Immunol 4:336–347

    Article  CAS  PubMed  Google Scholar 

  2. Nishimura H, Minato N, Nakano T, Honjo T (1998) Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol 10:1563–1572

    Article  CAS  PubMed  Google Scholar 

  3. Watanabe N, Gavrieli M, Sedy JR, Yang J, Fallarino F, Loftin SK, Hurchla MA, Zimmerman N, Sim J, Zang X (2003) BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1. Nat Immunol 4:670–679

    Article  CAS  PubMed  Google Scholar 

  4. Han P, Goularte OD, Rufner K, Wilkinson B, Kaye J (2004) An inhibitory Ig superfamily protein expressed by lymphocytes and APCs is also an early marker of thymocyte positive selection. J Immunol 172:5931–5939

    CAS  PubMed  Google Scholar 

  5. Carreno BM, Collins M (2003) BTLA: a new inhibitory receptor with a B7-like ligand. Trends Immunol 24:524–527

    Article  CAS  PubMed  Google Scholar 

  6. Sedy JR, Gavrieli M, Potter KG, Hurchla MA, Lindsley RC, Hildner K, Scheu S, Pfeffer K, Ware CF, Murphy TL (2005) B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator. Nat Immunol 6:90–98

    Article  CAS  PubMed  Google Scholar 

  7. Gonzalez LC, Loyet KM, Calemine-Fenaux J, Chauhan V, Wranik B, Ouyang W, Eaton DL (2005) A coreceptor interaction between the CD28 and TNF receptor family members B and T lymphocyte attenuator and herpesvirus entry mediator. Proc Natl Acad Sci U S A 102:1116–1121

    Article  CAS  PubMed  Google Scholar 

  8. Hamajima N (2001) PCR-CTPP: a new genotyping technique in the era of genetic epidemiology. Expert Rev Mol Diagn 1:119–123

    Article  CAS  PubMed  Google Scholar 

  9. Shastry BS (2002) SNP alleles in human disease and evolution. J Hum Genet 47:561–566

    Article  CAS  PubMed  Google Scholar 

  10. Wjst M (2004) Target SNP selection in complex disease association studies. BMC Bioinformatics 5:92

    Article  PubMed  Google Scholar 

  11. Gavrieli M, Murphy KM (2006) Association of Grb-2 and PI3K p85 with phosphotyrosile peptides derived from BTLA. Biochem Biophys Res Commun 345:1440–1445

    Article  CAS  PubMed  Google Scholar 

  12. Chemnitz JM, Lanfranco AR, Braunstein I, Riley JL (2006) B and T lymphocyte attenuator-mediated signal transduction provides a potent inhibitory signal to primary human CD4 T cells that can be initiated by multiple phosphotyrosine motifs. J Immunol 176:6603–6614

    CAS  PubMed  Google Scholar 

  13. Hurchla MA, Sedy JR, Gavrieli M, Drake CG, Murphy TL, Murphy KM (2005) B and T lymphocyte attenuator exhibits structural and expression polymorphisms and is highly Induced in anergic CD4+ T cells. J Immunol 174:3377–3385

    CAS  PubMed  Google Scholar 

  14. Lin SC, Kuo CC, Chan CH (2006) Association of a BTLA gene polymorphism with the risk of rheumatoid arthritis. J Biomed Sci 13:853–860

    Article  CAS  PubMed  Google Scholar 

  15. Tanrikulu S, Erbil Y, Ademoglu E, Issever H, Barbaros U, Kutluturk F, Ozarmagan S, Tezelman S (2006) The predictive value of CTLA-4 and Tg polymorphisms in the recurrence of Graves’ disease after antithyroid withdrawal. Endocrine 30:377–381

    Article  CAS  PubMed  Google Scholar 

  16. Erfani N, Razmkhah M, Talei AR, Pezeshki AM, Doroudchi M, Monabati A, Ghaderi A (2006) Cytotoxic T lymphocyte antigen-4 promoter variants in breast cancer. Cancer Genet Cytogenet 165:114–120

    Article  CAS  PubMed  Google Scholar 

  17. Lee SH, Lee YA, Woo DH, Song R, Park EK, Ryu MH, Kim YH, Kim KS, Hong SJ, Yoo MC et al (2006) Association of the programmed cell death 1 (PDCD1) gene polymorphism with ankylosing spondylitis in the Korean population. Arthritis Res Ther 8:R163

    Article  PubMed  Google Scholar 

  18. Jonsson JJ, Foresman MD, Wilson N, McIvor RS (1992) Intron requirement for expression of the human purine nucleoside phosphorylase gene. Nucleic Acids Res 20:3191–3198

    Article  CAS  PubMed  Google Scholar 

  19. Majewski J, Ott J (2002) Distribution and characterization of regulatory elements in the human genome. Genome Res 12:1827–1836

    Article  CAS  PubMed  Google Scholar 

  20. Baralle D, Baralle M (2005) Splicing in action: assessing disease causing sequence changes. J Med Genet 42:737–748

    Article  CAS  PubMed  Google Scholar 

  21. Krauss V, Pecyna M, Kurz K, Sass H (2005) Phylogenetic mapping of intron positions: a case study of translation initiation factor eIF2gamma. Mol Biol Evol 22:74–84

    Article  CAS  PubMed  Google Scholar 

  22. Watts TH (2005) TNF/TNFR family members in costimulation of T cell responses. Annu Rev Immunol 23:23–68

    Article  CAS  PubMed  Google Scholar 

  23. Bauer KR, Brown M, Cress RD, Parise CA, Caggiano V (2007) Descriptive analysis of estrogen receptor (ER)-negative, progesterone receptor (PR)-negative, and HER2-negative invasive breast cancer, the so-called triple-negative phenotype: a population-based study from the California cancer Registry. Cancer 109:1721–1728

    Article  PubMed  Google Scholar 

  24. Lee JS, Lo PK, Fackler MJ, Argani P, Zhang Z, Garrett-Mayer E, Sukumar S (2007) A Comparative Study of Korean with Caucasian Breast Cancer Reveals Frequency of Methylation in Multiple Genes Correlates with Breast Cancer in Young, ER, PR-negative Breast Cancer in Korean Women. Cancer Biol Ther 6:1114–1120

    Article  CAS  PubMed  Google Scholar 

  25. Stendahl M, Ryden L, Nordenskjold B, Jonsson PE, Landberg G, Jirstrom K (2006) High progesterone receptor expression correlates to the effect of adjuvant tamoxifen in premenopausal breast cancer patients. Clin Cancer Res 12:4614–4618

    Article  CAS  PubMed  Google Scholar 

  26. Beenken SW, Grizzle WE, Crowe DR, Conner MG, Weiss HL, Sellers MT, Krontiras H, Urist MM, Bland KI (2001) Molecular biomarkers for breast cancer prognosis: coexpression of c-erbB-2 and p53. Ann Surg 233:630–638

    Article  CAS  PubMed  Google Scholar 

  27. Shimizu C, Fukutomi T, Tsuda H, Akashi-Tanaka S, Watanabe T, Nanasawa T, Sugihara K (2000) c-erbB-2 protein overexpression and p53 immunoreaction in primary and recurrent breast cancer tissues. J Surg Oncol 73:17–20

    Article  CAS  PubMed  Google Scholar 

  28. Rudolph P, Alm P, Olsson H, Heidebrecht HJ, Ferno M, Baldetorp B, Parwaresch R (2001) Concurrent overexpression of p53 and c-erbB-2 correlates with accelerated cycling and concomitant poor prognosis in node-negative breast cancer. Hum Pathol 32:311–319

    Article  CAS  PubMed  Google Scholar 

  29. Logullo AF, Lopes AB, Nonogaki S, Soares FA, Netto MM, Nishimoto IN, Brentani MM (2007) C-erbB-2 expression is a better predictor for survival than galectin-3 or p53 in early-stage breast cancer. Oncol Rep 18:121–126

    PubMed  Google Scholar 

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Acknowledgements

Zhenkun Fu performed the primer design and wrote the drafts. Dalin Li collected the patient and control blood samples. Wei Jiang contributed statistical analysis. Lihong Wang, Jie Zhang and Fengyan Xu performed the PCR-RFLP and PCR-CTPP experiments. Da Pang and Dianjun Li conceived of the study, and participated in its design and coordination and helped to draft the article. All authors read and approved the final article. This study was supported by a grant from the Foundation of Education Department, Heilongjiang Province (11541180), the Innovative Fund of Heilongjiang Province Graduate Student (YJSCX2009-220HLJ) and the Innovative Fund of Harbin Medical University Graduate Student (HCXB2009013). 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.

Competing interests

The author(s) declare that they have no competing interests.

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Authors and Affiliations

  1. Department of Immunology, Harbin Medical University, 150081, Harbin, China

    Zhenkun Fu, Jie Zhang, Fengyan Xu & Dianjun Li

  2. Department of Surgery, The Third Affiliated Hospital of Harbin Medical University, 150081, Harbin, China

    Dalin Li & Da Pang

  3. Department of Bioinformatics, Harbin Medical University, 150081, Harbin, China

    Wei Jiang

  4. Institute of Cancer Prevention and Treatment, Harbin Medical University, 150081, Harbin, China

    Lihong Wang, Da Pang & Dianjun Li

Authors
  1. Zhenkun Fu
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  2. Dalin Li
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  3. Wei Jiang
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  7. Da Pang
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Correspondence to Da Pang or Dianjun Li.

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Fu, Z., Li, D., Jiang, W. et al. Association of BTLA gene polymorphisms with the risk of malignant breast cancer in Chinese women of Heilongjiang Province. Breast Cancer Res Treat 120, 195–202 (2010). https://doi.org/10.1007/s10549-009-0462-6

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  • DOI: https://doi.org/10.1007/s10549-009-0462-6

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