Genetic risk and gastric cancer: polygenic risk scores in population-based case-control study

ABSTRACTObjective This study aimed to screen and identify common variants and long noncoding RNA (lncRNA) single nucleotide polymorphisms (SNPs) associated with gastric cancer risk, and construct prediction models based on polygenic risk score (PRS).Methods The risk factors associated with gastric cancer were screened following meta-analysis and bioinformatics, verified by population-based case-control study. We constructed PRS and weighted genetic risk scores (wGRS) derived from the validation data set. Net reclassification improvement (NRI), integrated discrimination improvement (IDI), Akaike information criterion (AIC) and Bayesian information criterion (BIC) were used to evaluate model.Results The PRS was divided into 10 quantiles, with the 40–60% quantile as a reference. A risk gradient was revealed across quantile of the PRS, the risk of gastric cancer in the highest 10 quantile of PRS was 3.24-fold higher than that in control population (OR = 3.24, 95%CI: 2.07, 5.06). For NRI and IDI, PRS combinations were significantly improved compared to wGRS model combinations (P < 0.001). The model of PRS combined with lncRNA SNPs, smoking, drinking and Helicobacter pylori infection was the best-fitting model (AIC = 117.23, BIC = 122.31).Conclusion The model based on PRS combined with lncRNA SNPs, H. pylori infection, smoking, and drinking had the optimal predictive ability for gastric cancer risk, which was helpful to distinguish high-risk groups.KEYWORDS: Gastric cancerMeta-analysisIncidence riskRisk factorPolygenic risk score Declaration of interestThe authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.Reviewers disclosurePeer reviewers on this manuscript have no relevant financial relationships or otherwise to disclose.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/14737159.2023.2206957Additional informationFundingThis work was supported by grants from the National Natural Science Foundation of China (No. 81672917), Henan Province young and middle-aged health science and technology innovation excellent young talent training project (YXKC2022044).