基质细胞来源的 SPP1 和 SPARC 基因多态性与甲状腺乳头状癌易感性相关。

Polymorphisms in matricellular SPP1 and SPARC contribute to susceptibility to papillary thyroid cancer.

机构信息

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Head and Neck, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.

Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China; Department of Molecular Diagnostics, Sun Yat-Sen University Cancer Center, Guangzhou 510060, China.

出版信息

Genomics. 2020 Nov;112(6):4959-4967. doi: 10.1016/j.ygeno.2020.09.018. Epub 2020 Sep 9.

DOI:10.1016/j.ygeno.2020.09.018

PMID:32919020

Abstract

There is a compelling need to identify novel genetic variants for papillary thyroid cancer (PTC) susceptibility. The Cancer Genome Atlas (TCGA) data showed associations between SPP1 and SPARC mRNA overexpression and aggressive behaviors of PTC, which prompted us to assess potential associations between genetic variants in these genes and PTC risk. Three highly linked SPARC loci (rs1054204, rs3210714, and rs3549) contributed to reduced PTC risk under a codominant model (odds ratio [OR], 0.79-0.80). Variant CAG alleles at these loci significantly enhanced SPARC transcription activation upon cotransfection with miR-29b and miR-495 when compared to the common alleles GGC (all P < 0.05). The three SPARC polymorphisms interacted with SPP1 rs4754, with elevated joint ORs of 2.43, 2.52, and 2.52, respectively. Additionally, interaction between SPP1 rs2358744 and SPARC rs2304052 was observed. Our study revealed associations between SPP1 and SPARC polymorphisms that, individually or in combination, are involved in PTC susceptibility.

摘要

迫切需要鉴定新的甲状腺乳头癌（PTC）易感性的遗传变异。癌症基因组图谱（TCGA）数据显示，SPP1 和 SPARC mRNA 过表达与 PTC 的侵袭性行为之间存在关联，这促使我们评估这些基因中的遗传变异与 PTC 风险之间的潜在关联。三个高度连锁的 SPARC 基因座（rs1054204、rs3210714 和 rs3549）在共显性模型下降低了 PTC 风险（比值比 [OR]，0.79-0.80）。与常见等位基因 GGC 相比，这些基因座的变体 CAG 等位基因在与 miR-29b 和 miR-495 共转染时显著增强了 SPARC 的转录激活（均 P<0.05）。三个 SPARC 多态性与 SPP1 rs4754 相互作用，联合比值比分别升高了 2.43、2.52 和 2.52。此外，还观察到 SPP1 rs2358744 和 SPARC rs2304052 之间的相互作用。我们的研究揭示了 SPP1 和 SPARC 多态性之间的关联，这些多态性单独或组合参与了 PTC 的易感性。