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

Abstract

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

CLC Number:

R730.2

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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Relationships between gastric cancer and SNPs of autophagy-related genes on the PI3K/Akt/mTOR pathway

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