Liang Lina, Lu Guanming, Pan Guogang, Deng Yibin, Liang Jiadong, Liang Limei, Liu Jia, Tang Yujin, Wei Guijiang
Department of Medical Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Department of Breast and Thyroid Surgery, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, China.
Front Oncol. 2019 Dec 20;9:1415. doi: 10.3389/fonc.2019.01415. eCollection 2019.
Secreted phosphoprotein-1 (SPP1) has been reported to be involved in the pathogenesis of breast cancer (BRC), but the influence of SPP1 single nucleotide polymorphisms on the BRC susceptibility has been rarely reported. In this study, we explored the association between rs11730582, rs2853750, and rs35893069 in the SPP1 gene and the BRC susceptibility. We used Snapshot assay to detect SPP1 single nucleotide polymorphisms in 471 BRC patients and 471 controls. The plasma SPP1 level was measured by ELISA. We found that the CC genotype and C allele of rs11730582 were associated with a significantly decreased BRC risk compared with the TT genotype and T allele, respectively [CC vs. TT: odds ratio (OR) = 0.59, 95% CI = 0.37-0.94, = 0.026; C vs. T: OR = 0.79, 95% CI = 0.65-0.96, = 0.022]. In addition, BRC patients and controls with the rs11730582 CC genotype had a lower plasma SPP1 level than did BRC patients and controls with TT genotype ( = 0.007 and = 0.011, respectively). Moreover, the proportions of rs11730582 CC genotype and C allele were decreased in BRC patients with clinical stages I-III compared with those with clinical stage IV ( = 0.012 and = 0.003, respectively). Besides, the C-G-T haplotype was associated with a significantly decreased BRC risk compared with the T-A-T haplotype (OR = 0.69, 95% CI = 0.52-0.93, = 0.015). However, there was no significant association between rs2853750 or rs35893069 and the BRC risk. In summary, our study found the association between rs11730582 and the risk of BRC and suggested that rs11730582 may promote the occurrence and development of BRC by regulating SPP1 expression.
据报道,分泌型磷蛋白-1(SPP1)参与乳腺癌(BRC)的发病机制,但SPP1单核苷酸多态性对BRC易感性的影响鲜有报道。在本研究中,我们探讨了SPP1基因中的rs11730582、rs2853750和rs35893069与BRC易感性之间的关联。我们使用Snapshot检测法对471例BRC患者和471例对照进行SPP1单核苷酸多态性检测。采用酶联免疫吸附测定法(ELISA)测量血浆SPP1水平。我们发现,与TT基因型和T等位基因相比,rs11730582的CC基因型和C等位基因与BRC风险显著降低相关[CC与TT:比值比(OR)=0.59,95%置信区间(CI)=0.37-0.94,P=0.026;C与T:OR=0.79,95%CI=0.65-0.96,P=0.022]。此外,rs11730582 CC基因型的BRC患者和对照的血浆SPP1水平低于TT基因型的BRC患者和对照(分别为P=0.007和P=0.011)。此外,与临床分期为IV期的BRC患者相比,临床分期为I-III期的BRC患者中rs11730582 CC基因型和C等位基因的比例降低(分别为P=0.012和P=0.003)。此外,与T-A-T单倍型相比,C-G-T单倍型与BRC风险显著降低相关(OR=0.69,95%CI=0.52-0.93,P=0.015)。然而,rs2853750或rs35893069与BRC风险之间无显著关联。总之,我们的研究发现了rs11730582与BRC风险之间的关联,并表明rs11730582可能通过调节SPP1表达促进BRC的发生发展。