通过……的多基因风险评分预测胃癌风险

Prediction of gastric cancer risk by a polygenic risk score of .

作者信息

Wang Xiao-Yu, Wang Li-Li, Liang Shu-Zhen, Yang Chao, Xu Lin, Yu Meng-Chao, Wang Yi-Xuan, Dong Quan-Jiang

机构信息

Central Laboratories and Department of Gastroenterology, Qingdao Municipal Hospital, Qingdao University, Qingdao 266071, Shandong Province, China.

The Center for Microbes, Development and Health, CAS Key Laboratory of Molecular Virology and Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200000, China.

出版信息

World J Gastrointest Oncol. 2022 Sep 15;14(9):1844-1855. doi: 10.4251/wjgo.v14.i9.1844.

DOI:10.4251/wjgo.v14.i9.1844

PMID:36187384

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9516638/

Abstract

BACKGROUND

Genetic variants of () are involved in gastric cancer occurrence. Single nucleotide polymorphisms (SNPs) of that are associated with gastric cancer have been reported. The combined effect of SNPs on the risk of gastric cancer remains unclear.

AIM

To assess the performance of a polygenic risk score (PRS) based on SNPs in predicting the risk of gastric cancer.

METHODS

A total of 15 gastric cancer-associated SNPs were selected. The associations between these SNPs and gastric cancer were further validated in 1022 global strains with publicly available genome sequences. The PRS model was established based on the validated SNPs. The performance of the PRS for predicting the risk of gastric cancer was assessed in global strains using quintiles and random forest (RF) methods. The variation in the performance of the PRS among different populations of was further examined.

RESULTS

Analyses of the association between selected SNPs and gastric cancer in the global dataset revealed that the risk allele frequencies of six SNPs were significantly higher in gastric cancer cases than non-gastric cancer cases. The PRS model constructed subsequently with these validated SNPs produced significantly higher scores in gastric cancer. The odds ratio (OR) value for gastric cancer gradually increased from the first to the fifth quintile of PRS, with the fifth quintile having an OR value as high as 9.76 (95% confidence interval: 5.84-16.29). The results of RF analyses indicated that the area under the curve (AUC) value for classifying gastric cancer and non-gastric cancer was 0.75, suggesting that the PRS based on SNPs was capable of predicting the risk of gastric cancer. Assessing the performance of the PRS among different populations demonstrated that it had good predictive power for cancer risk for hpEurope strains, with an AUC value of 0.78.

CONCLUSION

The PRS model based on SNPs had a good performance for assessment of gastric cancer risk. It would be useful in the prediction of final consequences of the infection and beneficial for the management of the infection in clinical settings.

摘要

背景

（）的基因变异与胃癌的发生有关。已报道了与胃癌相关的（）单核苷酸多态性（SNP）。（）SNP对胃癌风险的综合影响仍不清楚。

目的

评估基于（）SNP的多基因风险评分（PRS）预测胃癌风险的性能。

方法

共选择了15个与胃癌相关的（）SNP。在1022个具有公开可用基因组序列的全球菌株中进一步验证了这些SNP与胃癌之间的关联。基于经过验证的SNP建立了PRS模型。使用五分位数和随机森林（RF）方法在全球菌株中评估PRS预测胃癌风险的性能。进一步研究了PRS在不同（）人群中的性能差异。

结果

对全球数据集中选定的SNP与胃癌之间的关联分析表明，6个SNP的风险等位基因频率在胃癌病例中显著高于非胃癌病例。随后用这些经过验证的SNP构建的PRS模型在胃癌中产生了显著更高的分数。胃癌的优势比（OR）值从PRS的第一个五分位数到第五个五分位数逐渐增加，第五个五分位数的OR值高达9.76（95%置信区间：5.84 - 16.29）。RF分析结果表明，区分胃癌和非胃癌的曲线下面积（AUC）值为0.75，表明基于（）SNP的PRS能够预测胃癌风险。评估PRS在不同（）人群中的性能表明，它对hpEurope菌株的癌症风险具有良好的预测能力，AUC值为0.78。