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Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study

Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian...

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Autores principales: Zhang, Xuening, Zhao, Hao, Man, Jinyu, Yin, Xiaolin, Zhang, Tongchao, Yang, Xiaorong, Lu, Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370260/
https://www.ncbi.nlm.nih.gov/pubmed/35956413
http://dx.doi.org/10.3390/nu14153237
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author Zhang, Xuening
Zhao, Hao
Man, Jinyu
Yin, Xiaolin
Zhang, Tongchao
Yang, Xiaorong
Lu, Ming
author_facet Zhang, Xuening
Zhao, Hao
Man, Jinyu
Yin, Xiaolin
Zhang, Tongchao
Yang, Xiaorong
Lu, Ming
author_sort Zhang, Xuening
collection PubMed
description Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian randomization (MR) study. Single nucleotide polymorphisms of diet-derived circulating antioxidants (i.e., α- and γ-tocopherol, ascorbate, retinol, β-carotene, lycopene, and urate), accessed by absolute levels and relative metabolite concentrations, were used as genetic instruments. Summary statistics for digestive system cancers were obtained from the UK Biobank and FinnGen studies. Two-sample MR analyses were performed in each of the two outcome databases, followed by a meta-analysis. The inverse-variance weighted MR was adopted as the primary analysis. Five additional MR methods (likelihood-based MR, MR-Egger, weighted median, penalized weighted median, and MR-PRESSO) and replicate MR analyses for outcomes from different sources were used as sensitivity analyses. Genetically determined antioxidants were not significantly associated with five digestive system cancers, after correcting for multiple tests. However, we found suggestive evidence that absolute ascorbate levels were negatively associated with colon cancer in UK Biobank—the odds ratio (OR) per unit increase in ascorbate was 0.774 (95% confidence interval [CI] 0.608–0.985, p = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623–0.936, p = 0.010). Likewise, higher absolute retinol levels suggestively reduced the pancreatic cancer risk in FinnGen—the OR per 10% unit increase in ln-transformed retinol was 0.705 (95% CI 0.529–0.940, p = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584–0.955, p = 0.020). Sensitivity analyses verified the above suggestive evidence. Our findings suggest that higher levels of antioxidants are unlikely to be a causal protective factor for most digestive system cancers, except for the suggestive protective effects of ascorbate on colon cancer and of retinol on pancreatic cancer.
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spelling pubmed-93702602022-08-12 Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study Zhang, Xuening Zhao, Hao Man, Jinyu Yin, Xiaolin Zhang, Tongchao Yang, Xiaorong Lu, Ming Nutrients Article Molecular mechanisms and observational studies have found that diet-derived antioxidants are associated with digestive system cancers, whereas there is a lack of causal evidence from randomized clinical trials. In this study, we aimed to assess the causality of these associations through a Mendelian randomization (MR) study. Single nucleotide polymorphisms of diet-derived circulating antioxidants (i.e., α- and γ-tocopherol, ascorbate, retinol, β-carotene, lycopene, and urate), accessed by absolute levels and relative metabolite concentrations, were used as genetic instruments. Summary statistics for digestive system cancers were obtained from the UK Biobank and FinnGen studies. Two-sample MR analyses were performed in each of the two outcome databases, followed by a meta-analysis. The inverse-variance weighted MR was adopted as the primary analysis. Five additional MR methods (likelihood-based MR, MR-Egger, weighted median, penalized weighted median, and MR-PRESSO) and replicate MR analyses for outcomes from different sources were used as sensitivity analyses. Genetically determined antioxidants were not significantly associated with five digestive system cancers, after correcting for multiple tests. However, we found suggestive evidence that absolute ascorbate levels were negatively associated with colon cancer in UK Biobank—the odds ratio (OR) per unit increase in ascorbate was 0.774 (95% confidence interval [CI] 0.608–0.985, p = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623–0.936, p = 0.010). Likewise, higher absolute retinol levels suggestively reduced the pancreatic cancer risk in FinnGen—the OR per 10% unit increase in ln-transformed retinol was 0.705 (95% CI 0.529–0.940, p = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584–0.955, p = 0.020). Sensitivity analyses verified the above suggestive evidence. Our findings suggest that higher levels of antioxidants are unlikely to be a causal protective factor for most digestive system cancers, except for the suggestive protective effects of ascorbate on colon cancer and of retinol on pancreatic cancer. MDPI 2022-08-08 /pmc/articles/PMC9370260/ /pubmed/35956413 http://dx.doi.org/10.3390/nu14153237 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Zhang, Xuening
Zhao, Hao
Man, Jinyu
Yin, Xiaolin
Zhang, Tongchao
Yang, Xiaorong
Lu, Ming
Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study
title Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study
title_full Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study
title_fullStr Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study
title_full_unstemmed Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study
title_short Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study
title_sort investigating causal associations of diet-derived circulating antioxidants with the risk of digestive system cancers: a mendelian randomization study
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9370260/
https://www.ncbi.nlm.nih.gov/pubmed/35956413
http://dx.doi.org/10.3390/nu14153237
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