Cargando…
Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans
BACKGROUND: Metabolic biomarkers are reported to be associated with the risk of lung cancer (LC). However, the observed associations from epidemiological studies are either inconsistent or inconclusive. METHODS: The genetic summary data of high-density lipoprotein cholesterol (HDL), low-density lipo...
Autores principales: | , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10131379/ https://www.ncbi.nlm.nih.gov/pubmed/37101305 http://dx.doi.org/10.1186/s40001-023-01116-4 |
_version_ | 1785031165210525696 |
---|---|
author | Liu, Kai Wang, Shangshang Zhou, Yuhan Huang, Sha Liu, Yifan Song, Lijiang He, Zhengfu |
author_facet | Liu, Kai Wang, Shangshang Zhou, Yuhan Huang, Sha Liu, Yifan Song, Lijiang He, Zhengfu |
author_sort | Liu, Kai |
collection | PubMed |
description | BACKGROUND: Metabolic biomarkers are reported to be associated with the risk of lung cancer (LC). However, the observed associations from epidemiological studies are either inconsistent or inconclusive. METHODS: The genetic summary data of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) and those of the LC and its histological subtypes were retrieved from previous GWASs. We performed two-sample Mendelian randomization (MR) and multivariable MR analyses to examine the associations between genetically predicted metabolic biomarkers and LC in East Asians and Europeans. RESULTS: In East Asians, the inverse-variance weighted (IVW) method suggests that LDL (odds ratio [OR] = 0.799, 95% CI 0.712–0.897), TC (OR = 0.713, 95% CI 0.638–0.797), and TG (OR = 0.702, 95% CI 0.613–0.804) were significantly associated with LC after correction for multiple testing. For the remaining three biomarkers, we did not detect significant association with LC by any MR method. Multivariable MR (MVMR) analysis yielded an OR of 0.958 (95% CI 0.748–1.172) for HDL, 0.839 (95% CI 0.738–0.931) for LDL, 0.942 (95% CI 0.742–1.133) for TC, 1.161 (95% CI 1.070–1.252) for TG, 1.079 (95% CI 0.851–1.219) for FPG, and 1.101 (95% CI 0.922–1.191) for HbA1c. In Europeans, the univariate MR analyses did not detect significant association between exposures and outcomes. However, in MVMR analysis integrating circulating lipids and lifestyle risk factors (smoking, alcohol drinking, and body mass index), we found that TG was positively associated with LC in Europeans (OR = 1.660, 95% CI 1.060–2.260). Subgroup and sensitivity analysis yielded similar results to the main analyses. CONCLUSIONS: Our study provides genetic evidence that circulating levels of LDL was negatively associated with LC in East Asians, whereas TG was positively associated with LC in both populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-023-01116-4. |
format | Online Article Text |
id | pubmed-10131379 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-101313792023-04-27 Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans Liu, Kai Wang, Shangshang Zhou, Yuhan Huang, Sha Liu, Yifan Song, Lijiang He, Zhengfu Eur J Med Res Research BACKGROUND: Metabolic biomarkers are reported to be associated with the risk of lung cancer (LC). However, the observed associations from epidemiological studies are either inconsistent or inconclusive. METHODS: The genetic summary data of high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), total cholesterol (TC), triglyceride (TG), fasting plasma glucose (FPG), and glycated hemoglobin (HbA1c) and those of the LC and its histological subtypes were retrieved from previous GWASs. We performed two-sample Mendelian randomization (MR) and multivariable MR analyses to examine the associations between genetically predicted metabolic biomarkers and LC in East Asians and Europeans. RESULTS: In East Asians, the inverse-variance weighted (IVW) method suggests that LDL (odds ratio [OR] = 0.799, 95% CI 0.712–0.897), TC (OR = 0.713, 95% CI 0.638–0.797), and TG (OR = 0.702, 95% CI 0.613–0.804) were significantly associated with LC after correction for multiple testing. For the remaining three biomarkers, we did not detect significant association with LC by any MR method. Multivariable MR (MVMR) analysis yielded an OR of 0.958 (95% CI 0.748–1.172) for HDL, 0.839 (95% CI 0.738–0.931) for LDL, 0.942 (95% CI 0.742–1.133) for TC, 1.161 (95% CI 1.070–1.252) for TG, 1.079 (95% CI 0.851–1.219) for FPG, and 1.101 (95% CI 0.922–1.191) for HbA1c. In Europeans, the univariate MR analyses did not detect significant association between exposures and outcomes. However, in MVMR analysis integrating circulating lipids and lifestyle risk factors (smoking, alcohol drinking, and body mass index), we found that TG was positively associated with LC in Europeans (OR = 1.660, 95% CI 1.060–2.260). Subgroup and sensitivity analysis yielded similar results to the main analyses. CONCLUSIONS: Our study provides genetic evidence that circulating levels of LDL was negatively associated with LC in East Asians, whereas TG was positively associated with LC in both populations. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s40001-023-01116-4. BioMed Central 2023-04-26 /pmc/articles/PMC10131379/ /pubmed/37101305 http://dx.doi.org/10.1186/s40001-023-01116-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Liu, Kai Wang, Shangshang Zhou, Yuhan Huang, Sha Liu, Yifan Song, Lijiang He, Zhengfu Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans |
title | Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans |
title_full | Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans |
title_fullStr | Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans |
title_full_unstemmed | Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans |
title_short | Genetic associations between circulating metabolic biomarkers and lung cancer in East Asians and Europeans |
title_sort | genetic associations between circulating metabolic biomarkers and lung cancer in east asians and europeans |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10131379/ https://www.ncbi.nlm.nih.gov/pubmed/37101305 http://dx.doi.org/10.1186/s40001-023-01116-4 |
work_keys_str_mv | AT liukai geneticassociationsbetweencirculatingmetabolicbiomarkersandlungcancerineastasiansandeuropeans AT wangshangshang geneticassociationsbetweencirculatingmetabolicbiomarkersandlungcancerineastasiansandeuropeans AT zhouyuhan geneticassociationsbetweencirculatingmetabolicbiomarkersandlungcancerineastasiansandeuropeans AT huangsha geneticassociationsbetweencirculatingmetabolicbiomarkersandlungcancerineastasiansandeuropeans AT liuyifan geneticassociationsbetweencirculatingmetabolicbiomarkersandlungcancerineastasiansandeuropeans AT songlijiang geneticassociationsbetweencirculatingmetabolicbiomarkersandlungcancerineastasiansandeuropeans AT hezhengfu geneticassociationsbetweencirculatingmetabolicbiomarkersandlungcancerineastasiansandeuropeans |