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

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

Clinical Genetics

Research output: Contribution to journal › Article › Academic › peer-review

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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 language	English
Pages (from-to)	995-1002
Number of pages	8
Journal	European Journal of Clinical Nutrition
Volume	76
Issue number	7
Early online date	21 Jan 2022
DOIs	https://doi.org/10.1038/s41430-022-01078-6
Publication status	Published - 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.

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10.1038/s41430-022-01078-6

Cite this

Wu, Y., Xin, J., Loehrer, E. A., Jiang, X., Yuan, Q., Christiani, D. C., Shi, H., Liu, L., Li, S., Wang, M., Chu, H., Du, M., & Zhang, Z. (2022). High-density lipoprotein, low-density lipoprotein and triglyceride levels and upper gastrointestinal cancers risk: a trans-ancestry Mendelian randomization study. European Journal of Clinical Nutrition, 76(7), 995-1002. https://doi.org/10.1038/s41430-022-01078-6

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

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.",

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

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). {\textcopyright} 2022. The Author(s), under exclusive licence to Springer Nature Limited.",

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doi = "10.1038/s41430-022-01078-6",

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Wu, Y, Xin, J, Loehrer, EA, Jiang, X, Yuan, Q, Christiani, DC, Shi, H, Liu, L, Li, S, Wang, M, Chu, H, Du, M & Zhang, Z 2022, 'High-density lipoprotein, low-density lipoprotein and triglyceride levels and upper gastrointestinal cancers risk: a trans-ancestry Mendelian randomization study', European Journal of Clinical Nutrition, vol. 76, no. 7, pp. 995-1002. https://doi.org/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. / Wu, Yanling; Xin, Junyi; Loehrer, Elizabeth A et al.
In: European Journal of Clinical Nutrition, Vol. 76, No. 7, 07.2022, p. 995-1002.

Research output: Contribution to journal › Article › Academic › peer-review

TY - JOUR

T1 - High-density lipoprotein, low-density lipoprotein and triglyceride levels and upper gastrointestinal cancers risk

T2 - a trans-ancestry Mendelian randomization study

AU - Wu, Yanling

AU - Xin, Junyi

AU - Loehrer, Elizabeth A

AU - Jiang, Xia

AU - Yuan, Qianyu

AU - Christiani, David C

AU - Shi, Hanping

AU - Liu, Lingxiang

AU - Li, Shuwei

AU - Wang, Meilin

AU - Chu, Haiyan

AU - Du, Mulong

AU - Zhang, Zhengdong

N1 - 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.

PY - 2022/7

Y1 - 2022/7

N2 - 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.

AB - 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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U2 - 10.1038/s41430-022-01078-6

DO - 10.1038/s41430-022-01078-6

M3 - Article

C2 - 35064221

SN - 0954-3007

VL - 76

SP - 995

EP - 1002

JO - European Journal of Clinical Nutrition

JF - European Journal of Clinical Nutrition

IS - 7

ER -

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

Abstract

Bibliographical note

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