High-density lipoprotein, low-density lipoprotein and triglyceride levels and upper gastrointestinal cancers risk: a trans-ancestry Mendelian randomization study

Yanling Wu, Junyi Xin, Elizabeth A Loehrer, Xia Jiang, Qianyu Yuan, David C Christiani, Hanping Shi, Lingxiang Liu, Shuwei Li, Meilin Wang, Haiyan Chu*, Mulong Du*, Zhengdong Zhang*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

3 Citations (Scopus)

Abstract

OBJECTIVE: This study was conducted to explore the causal associations of high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglyceride (TG) with the risk of upper gastrointestinal cancers (esophageal cancer [EC] and gastric cancer [GC]).

METHODS: A total of 5623 Chinese and 4133 Europeans afforded the individual-level genotyping data, and 203,608 Japanese from Biobank Japan project and 393,926 Europeans from UK Biobank supported summary statistics of cancer genetic associations. Mendelian randomization (MR) analyses, including weighted genetic risk scores (wGRSs), inverse-variance weighted (IVW), weighted median and Egger-regression, were utilized to evaluate the causal effects of three blood lipids on upper gastrointestinal cancers risk.

RESULTS: There was no significantly causal relationships between three blood lipids and EC or GC risk among Chinese or Europeans but a potential causal association between TG and GC risk among Japanese (IVW: odds ratio [OR] = 1.11, P = 0.034; Phet = 0.679). In stratified subgroups, higher genetically predicted TG levels were causally associated with an increased risk of GC among Chinese males (wGRS: OR = 1.61, P = 0.021; IVW: OR = 1.57, P = 0.009; Phet = 0.653) and Japanese females (IVW: OR = 1.33, P = 0.024; Phet = 0.378).

CONCLUSION: This trans-ancestry MR study suggested null significant causality between serum HDL, LDL or TG and the risk of upper gastrointestinal cancers among Chinese and Europeans, but provided evidence for a causal role of TG involved in GC etiology in Japanese (especially females), which would support a prevention guide for high-risk groups of GC. Further research with more comprehensive information is needed to explore the underlying mechanism.

Original languageEnglish
Pages (from-to)995-1002
Number of pages8
JournalEuropean Journal of Clinical Nutrition
Volume76
Issue number7
Early online date21 Jan 2022
DOIs
Publication statusPublished - Jul 2022

Bibliographical note

ACKNOWLEDGEMENTS:
The authors gratefully acknowledge the participants and staff involved in the
development of dbGaP, Biobank Japan project and UK Biobank database for their
dedication and effort. This study was supported by the National Key R&D Program of
China (grants 2018YFC1313100, 2018YFC1313102), and partially by the National Key R&D
Program of China (2017YFC1309201), and the Priority Academic Program Development
of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine).

© 2022. The Author(s), under exclusive licence to Springer Nature Limited.

Fingerprint

Dive into the research topics of 'High-density lipoprotein, low-density lipoprotein and triglyceride levels and upper gastrointestinal cancers risk: a trans-ancestry Mendelian randomization study'. Together they form a unique fingerprint.

Cite this