Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study
Objective: Based on multistage metabolomic profiling and Mendelian randomization analyses, the current study identified plasma metabolites that predicted the risk of developing gastric cancer (GC) and determined whether key metabolite levels modified the GC primary prevention effects. Methods: Plasm...
Saved in:
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
China Anti-Cancer Association
2025-05-01
|
| Series: | Cancer Biology & Medicine |
| Subjects: | |
| Online Access: | https://www.cancerbiomed.org/content/22/5/525 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850169240121769984 |
|---|---|
| author | Mengyuan Wang Zhouyi Yin Hengmin Xu Zongchao Liu Sha Huang Wenhui Wu Yang Zhang Tong Zhou Weicheng You Kaifeng Pan Wenqing Li |
| author_facet | Mengyuan Wang Zhouyi Yin Hengmin Xu Zongchao Liu Sha Huang Wenhui Wu Yang Zhang Tong Zhou Weicheng You Kaifeng Pan Wenqing Li |
| author_sort | Mengyuan Wang |
| collection | DOAJ |
| description | Objective: Based on multistage metabolomic profiling and Mendelian randomization analyses, the current study identified plasma metabolites that predicted the risk of developing gastric cancer (GC) and determined whether key metabolite levels modified the GC primary prevention effects. Methods: Plasma metabolites associated with GC risk were identified through a case-control study. Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial (SIT), a nested case-control study of the Mass Intervention Trial in Linqu, Shandong province (MITS), China, the UK Biobank, and the FinnGen project. Results: A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population (SIT: HR = 1.26 per 1 SD change, 95% CI: 1.07–1.49; MITS: HR = 1.07, 95% CI: 1.00–1.14) and an increased gastric adenocarcinoma risk in FinnGen (OR = 1.68, 95% CI: 1.16–2.45). Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level (P-interaction = 0.098) and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level ( P-interaction = 0.02). Conclusions: Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention. Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms. |
| format | Article |
| id | doaj-art-eb07d36efba64a75a6f1c2b71050f4e3 |
| institution | OA Journals |
| issn | 2095-3941 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | China Anti-Cancer Association |
| record_format | Article |
| series | Cancer Biology & Medicine |
| spelling | doaj-art-eb07d36efba64a75a6f1c2b71050f4e32025-08-20T02:20:45ZengChina Anti-Cancer AssociationCancer Biology & Medicine2095-39412025-05-0122552553810.20892/j.issn.2095-3941.2024.0523Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization studyMengyuan Wang0Zhouyi Yin1Hengmin Xu2Zongchao Liu3Sha Huang4Wenhui Wu5Yang Zhang6Tong Zhou7Weicheng You8Kaifeng Pan9Wenqing Li10State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaKey Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaState Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing 100142, ChinaObjective: Based on multistage metabolomic profiling and Mendelian randomization analyses, the current study identified plasma metabolites that predicted the risk of developing gastric cancer (GC) and determined whether key metabolite levels modified the GC primary prevention effects. Methods: Plasma metabolites associated with GC risk were identified through a case-control study. Bi-directional two-sample Mendelian randomization analyses were performed to determine potential causal relationships utilizing the Shandong Intervention Trial (SIT), a nested case-control study of the Mass Intervention Trial in Linqu, Shandong province (MITS), China, the UK Biobank, and the FinnGen project. Results: A higher genetic risk score for plasma L-aspartic acid was significantly associated with an increased GC risk in the northern Chinese population (SIT: HR = 1.26 per 1 SD change, 95% CI: 1.07–1.49; MITS: HR = 1.07, 95% CI: 1.00–1.14) and an increased gastric adenocarcinoma risk in FinnGen (OR = 1.68, 95% CI: 1.16–2.45). Genetically predicted plasma L-aspartic acid levels also modified the GC primary prevention effects with the beneficial effect of Helicobacter pylori eradication notably observed among individuals within the top quartile of L-aspartic acid level (P-interaction = 0.098) and the beneficial effect of garlic supplementation only for those within the lowest quartile of L-aspartic acid level ( P-interaction = 0.02). Conclusions: Elevated plasma L-aspartic acid levels significantly increased the risk of developing GC and modified the effects of GC primary prevention. Further studies from other populations are warranted to validate the modification effect of plasma L-aspartic acid levels on GC prevention and to elucidate the underlying mechanisms.https://www.cancerbiomed.org/content/22/5/525gastric cancerplasma metabolitesmendelian randomizationl-aspartic acid |
| spellingShingle | Mengyuan Wang Zhouyi Yin Hengmin Xu Zongchao Liu Sha Huang Wenhui Wu Yang Zhang Tong Zhou Weicheng You Kaifeng Pan Wenqing Li Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study Cancer Biology & Medicine gastric cancer plasma metabolites mendelian randomization l-aspartic acid |
| title | Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study |
| title_full | Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study |
| title_fullStr | Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study |
| title_full_unstemmed | Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study |
| title_short | Plasma L-aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect: a multistage metabolomic profiling and Mendelian randomization study |
| title_sort | plasma l aspartic acid predicts the risk of gastric cancer and modifies the primary prevention effect a multistage metabolomic profiling and mendelian randomization study |
| topic | gastric cancer plasma metabolites mendelian randomization l-aspartic acid |
| url | https://www.cancerbiomed.org/content/22/5/525 |
| work_keys_str_mv | AT mengyuanwang plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT zhouyiyin plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT hengminxu plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT zongchaoliu plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT shahuang plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT wenhuiwu plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT yangzhang plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT tongzhou plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT weichengyou plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT kaifengpan plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy AT wenqingli plasmalasparticacidpredictstheriskofgastriccancerandmodifiestheprimarypreventioneffectamultistagemetabolomicprofilingandmendelianrandomizationstudy |