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Open Access Highly Accessed Research article

ICOS gene polymorphisms are associated with sporadic breast cancer: a case-control study

Fengyan Xu12, Dalin Li3, Qiujin Zhang1, Zhenkun Fu1, Jie Zhang1, Weiguang Yuan12*, Shuang Chen1, Da Pang23* and Dianjun Li12*

Author Affiliations

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

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

3 Department of Surgery, the Third Affiliated Hospital of Harbin Medical University, Harbin, 150081, China

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BMC Cancer 2011, 11:392  doi:10.1186/1471-2407-11-392

Published: 15 September 2011

Abstract

Background

Inducible costimulator (ICOS), a costimulatory molecular of the CD28 family, provides positive signal to enhance T cell proliferation. Its abnormal expression can disturb the immune response and entail an increased risk of cancer. To investigate whether single nucleotide polymorphisms (SNPs) in the ICOS gene are associated with sporadic breast cancer susceptibility and progression in Chinese women, a case-control study was conducted.

Methods

In the study cohort, we genotyped five SNPs (rs11889031, rs10932029, rs4675374, rs10183087 and rs10932037) in ICOS gene among 609 breast cancer patients and 665 age-matched healthy controls. Furthermore, the positive results were replicated in an independent validation cohort of 619 patients and 682 age-matched healthy controls. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was used to determine the genotypes.

Results

In rs10932029, compared with TT genotype and T allele, the CT genotype and C allele showed a significantly increased risk of breast cancer (P = 0.030, OR = 1.467, 95% CI 1.037-2.077; P = 0.017, OR = 1.481, 95% CI 1.070-2.049, respectively), and the associations were also significant in the validation cohort (P = 0.002, OR = 1.693, 95% CI 1.211-2.357; P = 0.003, OR = 1.607, 95% CI 1.171-2.204, respectively). Haplotype analysis showed that CTCAC haplotype containing rs10932029 T allele had a lower frequency in cases than in controls (P = 0.015), whereas haplotype CCCAC containing rs10932029 C allele was more common in cases than in controls (P = 0.013). In the analysis of clinicopathologic features, rs11889031 CT genotype and T allele were associated with progesterone receptor (PR) status and lymph node metastasis, which were further supported by our validation cohort. Moreover, some haplotypes were associated with estrogen receptor (ER) and PR statuses.

Conclusions

These results indicate that ICOS 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.