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

doi:10.1038/s41430-022-01078-6

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

Eur J Clin Nutr. 2022 Jul;76(7):995-1002. doi: 10.1038/s41430-022-01078-6. Epub 2022 Jan 21.

Authors

Yanling Wu^#^{1

2

3}, Junyi Xin^#^{1

2}, Elizabeth A Loehrer⁴, Xia Jiang⁵, Qianyu Yuan⁶, David C Christiani^{6

7}, Hanping Shi⁸, Lingxiang Liu⁹, Shuwei Li^{1

2}, Meilin Wang^{1

2}, Haiyan Chu^{10

11}, Mulong Du¹², Zhengdong Zhang^{13

14}

Affiliations

¹ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China.
² Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China.
³ Center for Disease Control and Prevention of Wuzhong District in Suzhou, Suzhou, China.
⁴ Department of Clinical Genetics, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
⁵ Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska Institute, Nobels vagen 13, Stockholm, Sweden.
⁶ Departments of Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, MA, 02115, USA.
⁷ Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA, 02114, USA.
⁸ Departments of Gastrointestinal Surgery and Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing, China.
⁹ Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
¹⁰ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China. chy_grape@njmu.edu.cn.
¹¹ Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. chy_grape@njmu.edu.cn.
¹² Department of Biostatistics, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. drdumulong@njmu.edu.cn.
¹³ Department of Environmental Genomics, Jiangsu Key Laboratory of Cancer Biomarkers, Prevention and Treatment, Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, China. drzdzhang@njmu.edu.cn.
¹⁴ Department of Genetic Toxicology, The Key Laboratory of Modern Toxicology of Ministry of Education, Center for Global Health, School of Public Health, Nanjing Medical University, Nanjing, China. drzdzhang@njmu.edu.cn.

^# Contributed equally.

PMID: 35064221
DOI: 10.1038/s41430-022-01078-6

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; P_het = 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; P_het = 0.653) and Japanese females (IVW: OR = 1.33, P = 0.024; P_het = 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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Gastrointestinal Neoplasms* / genetics
Humans
Lipids
Lipoproteins, HDL
Lipoproteins, LDL
Male
Mendelian Randomization Analysis*
Polymorphism, Single Nucleotide
Triglycerides

Substances

Lipids
Lipoproteins, HDL
Lipoproteins, LDL
Triglycerides