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中国汉族女性乳腺癌患者 IL-17A 和 IL-17F 多态性的关联分析。

Association analysis of IL-17A and IL-17F polymorphisms in Chinese Han women with breast cancer.

机构信息

Institute of Cancer Prevention and Treatment, Harbin Medical University, Harbin, China.

出版信息

PLoS One. 2012;7(3):e34400. doi: 10.1371/journal.pone.0034400. Epub 2012 Mar 26.

Abstract

BACKGROUND

Research into the etiology of breast cancer has recently focused on the role of the immunity and inflammation. The proinflammatory cytokines IL-17A and IL-17F can mediate inflammation and cancer. To evaluate the influences of IL-17A and IL-17F gene polymorphisms on the risk of sporadic breast cancer, a case-control study was conducted in Chinese Han women.

METHODOLOGY AND PRINCIPAL FINDINGS

We genotyped three single-nucleotide polymorphisms (SNPs) in IL-17A (rs2275913, rs3819025 and rs3748067) and five SNPs in IL-17F (rs7771511, rs9382084, rs12203582, rs1266828 and rs763780) to determine the haplotypes in 491 women with breast cancer and 502 healthy individuals. The genotypes were determined using the SNaPshot technique. The differences in the genotypic distribution between breast cancer patients and healthy controls were analyzed with the Chi-square test for trends. For rs2275913 in IL-17A, the frequency of the AA genotype was higher in patients than controls (P = 0.0016). The clinical features analysis demonstrated significant associations between IL-17 SNPs and tumor protein 53 (P53), progesterone receptor (PR), human epidermal growth factor receptor 2 (Her-2) and triple-negative (ER-/PR-/Her-2-) status. In addition, the haplotype analysis indicated that the frequency of the haplotype A(rs2275913)G(rs3819025)G(rs3748067), located in the IL-17A linkage disequilibrium (LD) block, was higher in patients than in controls (P = 0.0471 after correction for multiple testing).

CONCLUSIONS AND SIGNIFICANCE

Our results suggested that SNPs in IL-17A but not IL-17F were associated with the risk of breast cancer. Both IL-17A and IL-17F gene polymorphisms may provide valuable information for predicting the prognosis of breast cancer in Chinese women.

摘要

背景

最近,乳腺癌病因的研究集中在免疫和炎症的作用上。促炎细胞因子 IL-17A 和 IL-17F 可以介导炎症和癌症。为了评估 IL-17A 和 IL-17F 基因多态性对散发性乳腺癌风险的影响,我们在中国汉族女性中进行了病例对照研究。

方法和主要发现

我们对 IL-17A(rs2275913、rs3819025 和 rs3748067)中的三个单核苷酸多态性(SNP)和 IL-17F(rs7771511、rs9382084、rs12203582、rs1266828 和 rs763780)中的五个 SNP 进行基因分型,以确定 491 名乳腺癌患者和 502 名健康个体的单倍型。使用 SNaPshot 技术确定基因型。使用卡方趋势检验分析乳腺癌患者和健康对照者之间基因型分布的差异。对于 IL-17A 中的 rs2275913,患者的 AA 基因型频率高于对照组(P=0.0016)。临床特征分析表明,IL-17 多态性与肿瘤蛋白 53(P53)、孕激素受体(PR)、人表皮生长因子受体 2(Her-2)和三阴性(ER-/PR-/Her-2-)状态之间存在显著关联。此外,单体型分析表明,位于 IL-17A 连锁不平衡(LD)块中的单体型 A(rs2275913)G(rs3819025)G(rs3748067)的频率在患者中高于对照组(经多重检验校正后 P=0.0471)。

结论和意义

我们的结果表明,IL-17A 中的 SNP 而不是 IL-17F 与乳腺癌风险相关。IL-17A 和 IL-17F 基因多态性均可为预测中国女性乳腺癌预后提供有价值的信息。

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