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汉族人群 RAS 家族基因突变与甲状腺乳头状癌的交互作用分析。

Association analysis between the interaction of RAS family genes mutations and papillary thyroid carcinoma in the Han Chinese population.

机构信息

Nuclear Medicine Department, First Hospital of Jilin University, Changchun 130021, China.

Department of Epidemiology and Biostatistics, School of Public Health, Jilin University, Changchun 130021, China.

出版信息

Int J Med Sci. 2021 Jan 1;18(2):441-447. doi: 10.7150/ijms.50026. eCollection 2021.

Abstract

Papillary thyroid carcinoma (PTC) is the major subtype of thyroid cancer, accounting for 75%-85% of all thyroid malignancies. This study aimed to identify the association between the interactions of single nucleotide polymorphisms (SNPs) in RAS family genes and PTC in the Han Chinese population, to provide clues to the pathogenesis and potential therapeutic targets for PTC. Hap Map and NCBI-db SNP databases were used to retrieve SNPs. Haploview 4.2 software was used to filter SNPs based on specific parameters, six SNPs of RAS gene (KRAS-rs12427141, KRAS-rs712, KRAS-rs7315339, HRAS-rs12628, NRAS-rs14804 and NRAS-rs2273267) were genotyped by matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) in 673 PTC patients and 657 healthy controls, the interactive effect was evaluated by crossover analysis, logistic regression and GMDR software. We found that genetic mutation in rs712 have significant associations with PTC risk after Bonferroni correction (<0.001). The interaction between KRAS-rs12427141 and HRAS-rs12628 increased the risk of PTC (U=-2.119, <0.05), the interaction between KRAS-rs2273267 and HRAS-rs7315339 reduced the risk of PTC (U=2.195, <0.05). GMDR analysis showed that the two-factor model (KRAS-rs712, NRAS-rs2273267) was the best (=0.0107). Summarily, there are PTC-related interactions between RAS family genes polymorphisms in the Han Chinese population.

摘要

甲状腺癌(PTC)是甲状腺癌的主要亚型,占所有甲状腺恶性肿瘤的 75%-85%。本研究旨在鉴定 RAS 家族基因单核苷酸多态性(SNPs)与中国汉族人群 PTC 之间的关联,为 PTC 的发病机制和潜在治疗靶点提供线索。使用 Hap Map 和 NCBI-db SNP 数据库检索 SNPs。使用 Haploview 4.2 软件根据特定参数过滤 SNPs,使用基质辅助激光解吸/电离飞行时间质谱(MALDI-TOF-MS)对 673 例 PTC 患者和 657 例健康对照者的 RAS 基因(KRAS-rs12427141、KRAS-rs712、KRAS-rs7315339、HRAS-rs12628、NRAS-rs14804 和 NRAS-rs2273267)的 6 个 SNPs 进行基因分型,通过交叉分析、Logistic 回归和 GMDR 软件评估交互作用。我们发现,经过 Bonferroni 校正后,rs712 的基因突变与 PTC 风险显著相关(<0.001)。KRAS-rs12427141 与 HRAS-rs12628 的相互作用增加了 PTC 的风险(U=-2.119,<0.05),KRAS-rs2273267 与 HRAS-rs7315339 的相互作用降低了 PTC 的风险(U=2.195,<0.05)。GMDR 分析表明,两因素模型(KRAS-rs712、NRAS-rs2273267)是最佳模型(=0.0107)。总之,中国汉族人群 RAS 家族基因多态性与 PTC 相关存在相互作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/08ef/7757130/6988f38ac3c0/ijmsv18p0441g001.jpg

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