收稿日期: 2023-07-12
网络出版日期: 2023-12-19
基金资助
国家自然科学基金项目(81972998);中央高校基本科研业务费专项基金项目(2242023k30021)
Association of genetic variants of m6A binding protein with the risk of gastric cancer
Received date: 2023-07-12
Online published: 2023-12-19
目的 探讨YTHDF1 rs6011668、HNRNPA2B1 rs2070601和rs76558212的单核苷酸多态性（SNPs）与胃癌风险关联。 方法 收集胃癌病例457例，健康对照525例，采用结合多重PCR和高通量测序的Hi-SNP的基因分型方法对YTHDF1 rs6011668、HNRNPA2B1 rs2070601和rs76558212进行基因分型；使用χ2检验和logistic 回归分析SNPs与胃癌发病风险和临床进展的关联，使用多因素logistic 回归和Risk Score（RS）模型综合分析环境和遗传因素对胃癌发病的影响。 结果 YTHDF1 rs6011668 TT基因型携带者的胃癌发病风险是CC基因型携带者的3.075倍（95%CI：1.128 ~ 8.382，P = 0.028），是CC/TC基因型携带者2.961倍（95%CI：1.091 ~ 8.033，P = 0.033）；分层分析发现，TT基因型主要增加不饮茶者、吃腌制食物者和吃油炸食物者的胃癌发病风险（P < 0.05）；此外，TT基因型携带者增加胃癌浸润程度、淋巴结转移、远端转移和中晚期风险（P < 0.05）。综合环境与遗传因素，计算病例组和对照组的风险评分（RS），以RS四分位数分组发现，RS得分越高，胃癌发病风险越高。与RS ≤ Q25组相比，Q25 ≤ RS < Q50组、Q50 < RS < Q75组和RS ≥ Q75组胃癌的发病风险分别为3.090、9.731和 19.949。 结论 YTHDF1 rs6011668突变基因型可能与增加胃癌发病风险和推进临床进展有关，结合环境与遗传因素能更好地评估胃癌的发病风险。
关键词： 胃癌; N6-腺苷酸甲基化; YTH结构域家族蛋白1; 异质核核糖核蛋白A2B1; 单核苷酸多态性
陆欣苑 , 冯延璐 , 李洁 , 许思易 , 李成云 , 刘桐 , 王新华 , 梁戈玉 . N6-腺苷酸甲基化结合蛋白的遗传变异与胃癌风险关联分析[J]. 实用医学杂志, 2023 , 39(21) : 2834 -2842 . DOI: 10.3969/j.issn.1006-5725.2023.21.024
Objective To investigate the association between single nucleotide polymorphisms （SNPs） of YTHDF1 rs6011668， HNRNPA2B1 rs2070601 and rs76558212 with the risk of gastric cancer. Methods A total of 457 cases with gastric cancer and 525 healthy controls were collected. The candidate SNPs were genotyped using Hi?SNP genotyping methods by multiplex rounds of PCR and high-throughput sequencing； the association between the three SNPs with the risk of gastric cancer was analyzed by test and Logistic regression. Multifactorial logistic regression and Risk Score （RS） model was used to analyze the influence of environmental and genetic factors on the risk of gastric cancer. Results YTHDF1rs6011668 TT genotype carriers had 3.075 times higher risk of gastric cancer than CC genotype carriers （95% CI：1.128 ~ 8.382， P = 0.028）， and 2.961 times higher risk than CC/TC genotypes carriers （95% CI：1.091 ~ 8.033， P = 0.033）. Subgroups-analysis revealed that TT genotype mainly increased the risk of gastric cancer in non?tea drinkers， pickled food eaters and fried food eaters（P < 0.05）. In addition， TT genotype carriers had the increased risk of gastric cancer infiltration， lymph node metastasis， distal metastasis and intermediate to advanced stages（P < 0.05）. The RS of the case and control groups were calculated by combining environmental and genetic factors. The higher the RS score， the higher the risk of gastric cancer was found in the RS quartile groups. Compared with the RS < Q25 group， the risk of gastric cancer in the Q25 < RS < Q50， Q50 < RS < Q75 and RS ≥ Q75 groups was 3.090， 9.731 and 19.949， respectively. Conclusion The YTHDF1 rs6011668 mutant genotype may be associated with an increased risk and clinical progression of gastric cancer， and combining environmental and genetic factors could better assess the risk of gastric cancer.
Key words： gastric cancer; m6A; YTHDF1; HNRNPA2B1; single nucleotide polymorphism
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