Yanling Wu1,2,3, Junyi Xin1,2, Elizabeth A Loehrer4, Xia Jiang5, Qianyu Yuan6, David C Christiani6,7, Hanping Shi8, Lingxiang Liu9, Shuwei Li1,2, Meilin Wang1,2, Haiyan Chu10,11, Mulong Du12, Zhengdong Zhang13,14. 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.
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.
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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