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Association of CTLA-4 gene polymorphisms with sporadic breast cancer risk and clinical features in Han women of Northeast China

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Abstract

Cytotoxic T lymphocyte antigen-4 (CTLA-4) is an inhibitory molecule that plays a pivotal role in downregulating T-cell mediated immune responses. To determine the role of CTLA-4 in tumor immunity, and to validate previous results as well, we investigated four tag single nucleotide polymorphisms (SNPs) of CTLA-4 in a relatively large Chinese Han cohort from northeastern China. Genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism (PCR–RFLP) in 581 patients and 566 age-matched controls. Our data indicated that compared with the common genotype and allele of each SNP, the −1722 CC genotype and C allele showed an increased risk of breast cancer (P = 0.030, odds ratio (OR) = 1.457, 95% confidence internal (CI) 1.036–2.051; P = 0.024, OR = 1.214, 95% CI 1.026–1.436, respectively). The −1661 GG genotype and G allele were also associated with an increased risk of breast cancer (P = 0.018, OR = 1.396, 95% CI 1.058–1.843; P = 0.013, OR = 1.353, 95% CI 1.066–1.717, respectively). In the haplotype analysis, the CAAA haplotype showed a higher frequency in cases (P = 0.004), and this association remained significant after correcting the P value for multiple testing. Associations were shown between the SNPs of CTLA-4 and lymph node metastasis, estrogen receptor (ER), progesterone receptor (PR) and P53 statuses. These results indicate that some SNPs in the CTLA-4 gene may affect the risk of breast cancer and show that some SNPs are associated with breast cancer characteristics in Han women in northeastern China.

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Abbreviations

CTLA-4:

Cytotoxic T lymphocyte antigen-4

SNP:

Single nucleotide polymorphism

OR:

Odds ratio

CI:

Confidence interval

ER:

Estrogen receptor

PR:

Progesterone receptor

LN:

Lymph node

TZ:

Tumor size

PCR-RFLP:

Polymerase chain reaction-restriction fragment length polymorphism

HWE:

Hardy–Weinberg equilibrium

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Acknowledgments

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.

Conflict of interest

The authors declare that they have no competing interests.

Author information

Authors and Affiliations

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

    Dalin Li, Weiguang Yuan & Da Pang

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

    Qiujin Zhang, Fengyan Xu, Zhenkun Fu & Dianjun Li

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

    Weiguang Yuan, Dianjun Li & Da Pang

Authors
  1. Dalin Li
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  2. Qiujin Zhang
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  3. Fengyan Xu
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  4. Zhenkun Fu
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  5. Weiguang Yuan
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  6. Dianjun Li
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  7. Da Pang
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Corresponding authors

Correspondence to Dianjun Li or Da Pang.

Additional information

Dalin Li and Qiujin Zhang have contributed equally to this study.

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Li, D., Zhang, Q., Xu, F. et al. Association of CTLA-4 gene polymorphisms with sporadic breast cancer risk and clinical features in Han women of Northeast China. Mol Cell Biochem 364, 283–290 (2012). https://doi.org/10.1007/s11010-012-1228-8

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  • DOI: https://doi.org/10.1007/s11010-012-1228-8

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