Department of Immunology, Harbin Medical University, Harbin, Heilongjiang, PR China.
BMC Cancer. 2009 Nov 11;9:394. doi: 10.1186/1471-2407-9-394.
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.
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.
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.
These results suggest that B7-H4 gene polymorphism may contribute to the sporadic breast cancer risk and prognosis in Chinese Han women.
B7-H4 是 B7 家族的一种共抑制分子，能够抑制 T 细胞增殖、细胞因子分泌和细胞毒性的发展。B7-H4 在肿瘤组织中的表达水平高于正常组织，具有保护肿瘤免受抗肿瘤免疫反应的潜在作用。本病例对照研究旨在确定 B7-H4 基因多态性对中国东北地区汉族女性乳腺癌易感性和进展的潜在影响。
我们对 500 例乳腺癌病例和 504 例年龄匹配的对照个体进行了 B7-H4 三个变体（rs10754339、rs10801935 和 rs3738414）的基因分型，并对所有常见单倍型（频率≥1%）进行了标记。聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术用于确定基因型。
我们的数据表明，与每个 SNP 的常见基因型和等位基因相比，rs10754339AG 基因型和 G 等位基因显著增加了乳腺癌的风险（OR=1.455，95%CI1.119-1.892；OR=1.325，95%CI1.073-1.637）。rs10801935CC 基因型、rs3738414AA 基因型和 rs3738414A 等位基因与乳腺癌风险显著降低相关（OR=0.328，95%CI0.145-0.739；OR=0.412，95%CI0.203-0.835；OR=0.698，95%CI0.564-0.864）。此外，rs10754339GG 基因型与淋巴结转移和 PR 状态显著相关，G 等位基因和 AG 基因型与淋巴结转移和 ER 状态显著相关。在单倍型分析中，与 AAG 单倍型相比，我们观察到 AAA 单倍型显著降低了乳腺癌的风险（OR=0.689，95%CI0.539-0.881），但 GAG 单倍型与乳腺癌的风险显著增加相关（OR=1.511，95%CI1.125-2.031）。此外，AAA 和 GCG 单倍型也分别对肿瘤大小和 ER 状态有显著影响。
这些结果表明，B7-H4 基因多态性可能导致中国汉族女性散发性乳腺癌的发病风险和预后。
