基于SNP芯片研究PI3K/Akt/mTOR通路上自噬相关基因SNPs与胃癌的关联

doi:10.3969/j.issn.1004-616x.2020.02.007

摘要/Abstract

摘要： 目的： 探讨与胃癌发生相关的PI3K/Akt/mTOR通路上新的与自噬相关基因单核苷酸多态性位点（SNPs），为寻找有价值的胃癌发生相关的分子标志物提供新的依据。方法： 采用1：1配对病例-对照研究的方法。通过KEGG pathway网站和Gene Ontology、Ensemble数据库及HaploView、STRING、Cytoscape软件联合SNP芯片筛选目标SNPs，采用基质辅助激光解吸电离飞行时间质谱（MALDI-TOF-MS）对筛检出来的SNPs位点在来自福建省仙游县的622例胃癌患者和622例健康人群基因组中进行验证。结果： SNP芯片及生物信息学分析筛选出IRS1 rs10205233、PIK3CD rs3934934、PIK3R1 rs706711、PIK3R1 rs706714和AKT1 rs35285446为候选位点。扩大样本验证发现IRS1 rs10205233的多态性变异（C > T）显著降低了胃癌的发病风险[共显性模型、显性模型的OR（95% CI）分别为0.761（0.595，0.975）、0.764（0.601，0.973）]。进一步分层分析，该位点显性模型、隐形模型、共显性模型以及等位基因在贲门癌和非贲门癌人群中均未见统计学差异（P > 0.05）。并未见其他位点与患胃癌风险的关联有统计学意义。对PIK3R1基因2个位点（rs706711、rs706714）的单体型分析也未见统计学差异。结论： IRS1 rs10205233位点与福建省胃癌高发区仙游县的胃癌发生存在关联，T等位基因可能是胃癌发生的一个遗传保护因素。

关键词: PI3K/Akt/mTOR通路, 自噬, 单核苷酸多态性, 胃癌

Abstract: OBJECTIVES: To explore new autophagy related single nucleotide polymorphisms (SNPs) on the PI3K/Akt/mTOR pathway and their association with gastric carcinogenesis. METHODS: A 1:1 matched case-control study was conducted. SNP microarray was combined with KEGG pathway,Gene Ontology and Ensemble database to screen target SNPs. Matrix-assisted laser desorption/Ionization time of flight mass spectrometry (MALDI-TOF-MS) was used to detect SNP loci in 622 patients with gastric cancer and 622 healthy individuals from the Xianyou county,Fujian province. RESULTS: SNP chip and bioinformatics analyses screened IRS1 rs10205233,PIK3CD rs3934934,PIK3R1 rs706711,PIK3R1 rs706714 and AKT1 rs35285446 as candidate sites. Validations using expanded samples found that the polymorphism of IRS1 rs10205233 (C > T) significantly reduced the risk of gastric cancer[OR(95%CI),with co-dominant and dominant models of 0.761 (0.595,0.975) and 0.764 (0.601,0.973)],respectively. Further stratification analyses show that the dominant,invisible,codominant models and alleles of the site were not statistically different among cardia cancer and non-cardia cancer patients (P > 0.05). There was no correlation between the other 4 loci and the haplotype of PIK3R1 (rs706711,rs706714) with susceptibility to gastric cancer (P > 0.05). CONCLUSION: The IRS1 rs10205233 locus was associated with gastric carcinogenesis in the Xianyou county,a high-risk area of gastric cancer in Fujian province. The T allele may be a genetic protective factor for gastric cancer.

Key words: PI3K/Akt/mTOR signal pathway, autophagy, single nucleotide polymorphism, gastric cancer

中图分类号:

R730.2

舒智雄, 吴传城, 吴晓丽, 刘宝英. 基于SNP芯片研究PI3K/Akt/mTOR通路上自噬相关基因SNPs与胃癌的关联[J]. 癌变·畸变·突变, 2020, 32(2): 118-125,131.

SHU Zhixiong, WU Chuancheng, WU Xiaoli, LIU Baoying. Relationships between gastric cancer and SNPs of autophagy-related genes on the PI3K/Akt/mTOR pathway[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2020, 32(2): 118-125,131.

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