Department of Immunology, Harbin Medical University, Harbin, China.
PLoS One. 2012;7(10):e48031. doi: 10.1371/journal.pone.0048031. Epub 2012 Oct 25.
CD28 is one of a number of costimulatory molecules that play crucial roles in immune regulation and homeostasis. Accumulating evidence indicates that immune factors influence breast carcinogenesis. To clarify the relationships between polymorphisms in the CD28 gene and breast carcinogenesis, a case-control study was conducted in women from Heilongjiang Province in northeast of China.
METHODOLOGY/PRINCIPAL FINDINGS: Our research subjects consisted of 565 female patients with sporadic breast cancer and 605 age- and sex-matched healthy controls. In total, 12 single nucleotide polymorphisms (SNPs) in the CD28 gene were successfully determined using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The relationship between the CD28 variants and clinical features, including histological grade, tumor size, lymph node metastasis, human epidermal growth factor receptor 2 (C-erbB2), estrogen receptor (ER), progesterone receptor (PR), and tumor protein 53 (P53) status were analyzed. A statistically significant association was observed between rs3116496 and breast cancer risk under different genetic models (additive P = 0.0164, dominant P = 0.0042). Different distributions of the rs3116496 'T' allele were found in patients and controls, which remained significant after correcting the P value for multiple testing using Haploview with 10,000 permutations (corrected P = 0.0384). In addition, significant associations were observed between rs3116487/rs3116494 (D' = 1, r(2) = 0.99) and clinicopathological features such as C-erbB2 and ER status, in breast cancer patients.
CONCLUSIONS/SIGNIFICANCE: Our findings indicate that CD28 gene polymorphisms contribute to sporadic breast cancer risk and have a significant association with clinicopathological features in a northeast Chinese Han population.
CD28 是许多共刺激分子之一，在免疫调节和稳态中起着至关重要的作用。越来越多的证据表明，免疫因素会影响乳腺癌的发生。为了阐明 CD28 基因多态性与乳腺癌发生之间的关系，在中国东北黑龙江省进行了一项病例对照研究。
方法/主要发现：我们的研究对象包括 565 名女性散发性乳腺癌患者和 605 名年龄和性别匹配的健康对照者。总共使用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法成功确定了 CD28 基因中的 12 个单核苷酸多态性（SNP）。分析了 CD28 变体与临床特征之间的关系，包括组织学分级、肿瘤大小、淋巴结转移、人表皮生长因子受体 2（C-erbB2）、雌激素受体（ER）、孕激素受体（PR）和肿瘤蛋白 53（P53）状态。在不同的遗传模型下，rs3116496 与乳腺癌风险之间存在统计学显著关联（加性 P=0.0164，显性 P=0.0042）。在患者和对照组中发现 rs3116496‘T’等位基因的分布不同，经过 Haploview 进行 10000 次随机检验校正多重检验 P 值后，该差异仍然具有统计学意义（校正 P=0.0384）。此外，在乳腺癌患者中，rs3116487/rs3116494（D'=1，r(2)=0.99）与 C-erbB2 和 ER 状态等临床病理特征之间存在显著关联。
结论/意义：我们的研究结果表明，CD28 基因多态性与散发性乳腺癌风险有关，并与中国东北地区汉族人群的临床病理特征有显著关联。
