高多基因风险评分与胃癌风险呈正相关，与韩国成年人的咖啡和多酚摄入量以及吸烟状况相互作用。

High Polygenic Risk Scores Positively Associated with Gastric Cancer Risk Interact with Coffee and Polyphenol Intake and Smoking Status in Korean Adults.

机构信息

Department of Chemical Engineering, Shanxi Institute of Science and Technology, Jincheng 048000, China.

Department of Food and Nutrition, Obesity/Diabetes Research Center, Hoseo University, Asan 31499, Republic of Korea.

出版信息

Nutrients. 2024 Sep 27;16(19):3263. doi: 10.3390/nu16193263.

DOI:10.3390/nu16193263

PMID:39408230

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11478441/

Abstract

BACKGROUND/OBJECTIVES: This study investigated the relationship between single nucleotide polymorphisms (SNPs) and gastric cancer (GC) risk, while also examining the interaction of genetic factors with lifestyle variables including the nutrient and bioactive compound intake in Korean adults of a large hospital-based cohort.

METHODS

We conducted a genome-wide association study (GWAS) comparing GC patients ( = 312) with healthy controls without cancers ( = 47,994) to identify relevant genetic variants. Generalized multifactor dimensionality reduction (GMDR) was employed to detect SNP interactions between diets and lifestyles. We utilized polygenic risk scores (PRSs) to assess individuals' GC risk based on multiple SNP loci. Among the selected SNPs, since _rs1527482 was a missense mutation, bioactive compounds which decrease the binding energy were found with its wild and mutated proteins by molecular docking analysis.

RESULTS

Individuals with high PRSs exhibited a 4.12-fold increased risk of GC compared to those with low PRSs. Additional factors associated with elevated GC risk included a low white blood cell count (OR = 5.13), smoking (OR = 3.83), and low coffee consumption (OR = 6.30). The _rs1527482 variant showed a positive correlation with GC risk. Molecular docking analyses suggested that certain polyphenols, including theaflavate, rugosin E, vitisifuran B, and plantacyanin, reduced the binding free energy in both wild-type and mutated _rs1527482. However, some polyphenols exhibited differential binding energies between its wild and mutated forms, suggesting they might modulate wild and mutated proteins differently.

CONCLUSION

High PRSs and _rs1527482 interact with immune function, coffee intake, polyphenol consumption, and smoking status to influence GC risk. These findings could contribute to developing personalized nutrition and lifestyle interventions to reduce GC risk.

摘要

背景/目的：本研究旨在探讨单核苷酸多态性（SNP）与胃癌（GC）风险之间的关系，并研究遗传因素与生活方式变量（包括营养素和生物活性化合物的摄入）之间的相互作用，在韩国一个大型基于医院的队列中。

方法

我们进行了一项全基因组关联研究（GWAS），将胃癌患者（n=312）与无癌症的健康对照者（n=47994）进行比较，以确定相关的遗传变异。广义多因子降维（GMDR）用于检测饮食和生活方式之间的 SNP 相互作用。我们利用多基因风险评分（PRSs）根据多个 SNP 位点评估个体的 GC 风险。在所选择的 SNP 中，由于 _rs1527482 是一个错义突变，通过分子对接分析发现了与其野生和突变蛋白结合能降低的生物活性化合物。

结果

与低 PRS 个体相比，高 PRS 个体的 GC 风险增加了 4.12 倍。与 GC 风险升高相关的其他因素包括白细胞计数低（OR=5.13）、吸烟（OR=3.83）和咖啡摄入量低（OR=6.30）。_rs1527482 变异与 GC 风险呈正相关。分子对接分析表明，某些多酚，包括茶黄素、芦丁 E、山奈黄素 B 和植物青素，降低了野生型和突变型 _rs1527482 的结合自由能。然而，一些多酚在其野生型和突变型之间表现出不同的结合能，表明它们可能以不同的方式调节野生型和突变型蛋白。