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.
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Data availability
Individual genotyping data of Chinese and European ancestry were obtained from dbGaP datasets (phs000361.v1.p1 and phs000869.v1.p1, respectively). Summary statistics of genetic associations with gastric cancer risk were extracted from UK Biobank single variant association analysis results at Lee Lab (https://www.leelabsg.org/resources). 1Shanxi and Linxian NIT: dbGaP, phs000361.v1.p1. 2BEAGESS: dbGaP, phs000869.v1.p1. 3BBJ GWAS summary statistics: http://jenger.riken.jp/en/result. 4UK Biobank GWAS summary statistics at Lee Lab: https://www.leelabsg.org/resources.
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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).
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ZZ, MD and HC are coresponders for this study. YW and JX contributed equally. ZZ, MD, JX and YW developed the study concept and design. YW and JX performed data analysis and interpretation. EL, XJ, QY, DC, HS, LL, MW, SL and HC assisted interpretation of results. YW and JX drafted the article. All authors revised the text and approved the final manuscript.
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Wu, Y., Xin, J., Loehrer, E.A. et al. High-density lipoprotein, low-density lipoprotein and triglyceride levels and upper gastrointestinal cancers risk: a trans-ancestry Mendelian randomization study. Eur J Clin Nutr 76, 995–1002 (2022). https://doi.org/10.1038/s41430-022-01078-6
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DOI: https://doi.org/10.1038/s41430-022-01078-6
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