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Open Access Highly Accessed Research article

B7-H4 gene polymorphisms are associated with sporadic breast cancer in a Chinese Han population

Jie Zhang13, Mingyan Zhang1, Wei Jiang2, Lihong Wang3, Zhenkun Fu1, Dalin Li4, Da Pang34* and Dianjun Li13*

Author Affiliations

1 Department of Immunology, Harbin Medical University, Harbin, Heilongjiang, PR China

2 Department of Bioinformatics, Harbin Medical University, Harbin, Heilongjiang, PR China

3 Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin, Heilongjiang, PR China

4 Department of Surgery, the Third Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, PR China

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BMC Cancer 2009, 9:394  doi:10.1186/1471-2407-9-394

Published: 11 November 2009

Abstract

Background

B7-H4, a co-inhibitory molecule of the B7 family, can restrain T cell proliferation, cytokine secretion and the development of cytotoxicity. B7-H4 is expressed in tumor tissues at a higher level than in normal tissues, and has a potential effect to protect tumors from anti-tumor immune responses. This case-control study was carried out to determine the potential influences of B7-H4 gene polymorphisms on the susceptibility and progression of breast cancer in Han women of Northeast China.

Methods

We genotyped three B7-H4 variants (rs10754339, rs10801935 and rs3738414) and tagged all common haplotypes (frequency greater than or equal to 1%) in a Chinese population consisting of 500 breast cancer cases and 504 control individuals matched for age. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was used to determine the genotypes.

Results

Our data indicated that, compared with the common genotype and allele of each SNP, the rs10754339 AG genotype and G allele showed a significantly increased risk of breast cancer (OR = 1.455, 95% CI 1.119-1.892; OR = 1.325, 95% CI 1.073-1.637, respectively). The rs10801935 CC genotype, the rs3738414 AA genotype and the rs3738414 A allele were associated with a significantly decreased risk of breast cancer (OR = 0.328, 95% CI 0.145-0.739; OR = 0.412, 95% CI 0.203-0.835; OR = 0.698, 95% CI 0.564-0.864, respectively). Additionally, the rs10754339 GG genotype was significantly associated with lymph node metastasis and PR status, and the G allele and the AG genotype were respectively associated with lymph node metastasis and ER status. In haplotype analysis, we observed that compared with the AAG haplotype, the AAA haplotype showed a significantly decreased risk of breast cancer (OR = 0.689, 95% CI 0.539-0.881), but the GAG haplotype was associated with a significantly increased risk of breast cancer (OR = 1.511, 95% CI 1.125-2.031). And the AAA and the GCG haplotypes also respectively have significant influences on tumor size and ER status.

Conclusion

These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.