دورية أكاديمية
Elucidating the role of blood metabolites on pancreatic cancer risk using two-sample Mendelian randomization analysis.
العنوان: | Elucidating the role of blood metabolites on pancreatic cancer risk using two-sample Mendelian randomization analysis. |
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المؤلفون: | Zhong H; Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA., Liu S; Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA., Zhu J; Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA., Xu TH; Torrey Pines High School, San Diego, California, USA., Yu H; Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA., Wu L; Cancer Epidemiology Division, Population Sciences in the Pacific Program, University of Hawaii Cancer Center, University of Hawaii at Manoa, Honolulu, Hawaii, USA. |
المصدر: | International journal of cancer [Int J Cancer] 2024 Mar 01; Vol. 154 (5), pp. 852-862. Date of Electronic Publication: 2023 Oct 20. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Wiley-Liss Country of Publication: United States NLM ID: 0042124 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1097-0215 (Electronic) Linking ISSN: 00207136 NLM ISO Abbreviation: Int J Cancer Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1995- : New York, NY : Wiley-Liss Original Publication: 1966-1984 : Genève : International Union Against Cancer |
مواضيع طبية MeSH: | Pancreatic Neoplasms*/genetics , Carcinoma, Pancreatic Ductal*/genetics, Humans ; Mendelian Randomization Analysis ; Genome-Wide Association Study ; Longitudinal Studies ; Canada/epidemiology |
مستخلص: | Pancreatic ductal adenocarcinoma (PDAC) is an uncommon but highly fatal malignancy. Identifying causal metabolite biomarkers offers an opportunity to facilitate effective risk assessment strategies for PDAC. In this study, we performed a two-sample Mendelian randomization (MR) study to characterize the potential causal effects of metabolites in plasma on PDAC risk. Genetic instruments were determined for a total of 506 metabolites from one set of comprehensive genome-wide association studies (GWAS) involving 913 individuals of European ancestry from the INTERVAL/EPIC-Norfolk cohorts. Another set of genetic instruments was developed for 483 metabolites from an independent GWAS conducted with 8299 individuals of European ancestry from the Canadian Longitudinal Study on Aging (CLSA) cohort. We analyzed GWAS data of the Pancreatic Cancer Cohort Consortium (PanScan) and the Pancreatic Cancer Case-Control Consortium (PanC4), comprising 8275 PDAC cases and 6723 controls of European ancestry. The association of metabolites with PDAC risk was assessed using the inverse-variance weighted (IVW) method, and complemented with sensitivity analyses of MR-Egger and MR-PRESSO tests. Potential side effects of targeting the identified metabolites for PDAC intervention were further evaluated by a phenome-wide MR (Phe-MR) analysis. Forty-four unique metabolites were identified to be significantly associated with PDAC risk, of which four top-ranking metabolites (X: 12798, X: 11787, X: 11308 and X: 19141) showed replication evidence when using instruments developed from both two cohorts. Our results highlight novel blood metabolites related to PDAC risk, which may help prioritize metabolic features for PDAC mechanistic research and further evaluation of their potential role in PDAC risk assessment. (© 2023 UICC.) |
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معلومات مُعتمدة: | R00 CA218892 United States CA NCI NIH HHS; T32 DK137523 United States DK NIDDK NIH HHS; U54 HG013243 United States HG NHGRI NIH HHS; R00CA218892 United States CA NCI NIH HHS |
فهرسة مساهمة: | Keywords: pancreatic ductal adenocarcinoma; plasma metabolites; risk; two-sample Mendelian randomization |
تواريخ الأحداث: | Date Created: 20231020 Date Completed: 20240105 Latest Revision: 20240526 |
رمز التحديث: | 20240526 |
مُعرف محوري في PubMed: | PMC10843029 |
DOI: | 10.1002/ijc.34771 |
PMID: | 37860916 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1097-0215 |
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DOI: | 10.1002/ijc.34771 |