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Open AccessHighly AccessResearch article

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

Jie Zhang1,3 email, Mingyan Zhang1 email, Wei Jiang2 email, Lihong Wang3 email, Zhenkun Fu1 email, Dalin Li4 email, Da Pang3,4 email and Dianjun Li1,3 email

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

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

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

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

author email corresponding author email

BMC Cancer 2009, 9:394doi: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.


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