Gastric Cancer Risk Prediction Using an Epidemiological Risk Assessment Model and Polygenic Risk Score

Simple Summary Risk prediction models incorporate various established risk factors to estimate individual risk specifically in cancer. These models additionally include biological or genetic risk factors to assess cancer risk more accurately. The polygenic risk score (PRS) combines the effects of multiple single-nucleotide polymorphisms (SNPs) that are associated with disease; its discrimination ability was assessed both alone and when used in combination with conventional risk prediction models. As few studies have evaluated the combination of genetic variants to identify high risk population of gastric cancer (GC), and we examined the performance of a GC risk assessment model in combination with SNPs as a PRS in consideration of Helicobacter pylori (H. pylori) infection status. Such a combination improves the identification of a GC-susceptible population among people with H. pylori infection. We investigated the performance of a gastric cancer (GC) risk assessment model in combination with single-nucleotide polymorphisms (SNPs) as a polygenic risk score (PRS) in consideration of Helicobacter pylori (H. pylori) infection status. Six SNPs identified from genome-wide association studies and a marginal association with GC in the study population were included in the PRS. Discrimination of the GC risk assessment model, PRS, and the combination of the two (PRS-GCS) were examined regarding incremental risk and the area under the receiver operating characteristic curve (AUC), with grouping according to H. pylori infection status. The GC risk assessment model score showed an association with GC, irrespective of H. pylori infection. Conversely, the PRS exhibited an association only for those with H. pylori infection. The PRS did not discriminate GC in those without H. pylori infection, whereas the GC risk assessment model showed a modest discrimination. Among individuals with H. pylori infection, discrimination by the GC risk assessment model and the PRS were comparable, with the PRS-GCS combination resulting in an increase in the AUC of 3%. In addition, the PRS-GCS classified more patients and fewer controls at the highest score quintile in those with H. pylori infection. Overall, the PRS-GCS improved the identification of a GC-susceptible population of people with H. pylori infection. In those without H. pylori infection, the GC risk assessment model was better at identifying the high-risk group.

Automated summary

Risk prediction models for cancer incorporate established and genetic risk factors to accurately estimate individual risk. This study examined the performance of a gastric cancer risk assessment model combined with SNPs as a polygenic risk score (PRS) in consideration of H. pylori infection. The combination of PRS with the risk assessment model improved identification of a high-risk population with H. pylori infection for gastric cancer susceptibility.