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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MDPI AG
2022-08-01
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| Online Access: | https://www.mdpi.com/2072-6643/14/15/3237 |
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| author | Xuening Zhang Hao Zhao Jinyu Man Xiaolin Yin Tongchao Zhang Xiaorong Yang Ming Lu |
| author_facet | Xuening Zhang Hao Zhao Jinyu Man Xiaolin Yin Tongchao Zhang Xiaorong Yang Ming Lu |
| author_sort | Xuening Zhang |
| collection | DOAJ |
| 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, <i>p</i> = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623–0.936, <i>p</i> = 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, <i>p</i> = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584–0.955, <i>p</i> = 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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| language | English |
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| spelling | doaj.art-d8fedb5b2e2247bfaf58b94166a0dee72023-12-03T12:54:27ZengMDPI AGNutrients2072-66432022-08-011415323710.3390/nu14153237Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization StudyXuening Zhang0Hao Zhao1Jinyu Man2Xiaolin Yin3Tongchao Zhang4Xiaorong Yang5Ming Lu6Department of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaDepartment of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou 510080, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaClinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan 250012, ChinaClinical Epidemiology Unit, Qilu Hospital of Shandong University, Jinan 250012, ChinaDepartment of Epidemiology and Health Statistics, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan 250012, ChinaMolecular 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, <i>p</i> = 0.037), which was consistent with the results in FinnGen, and the combined OR was 0.764 (95% CI 0.623–0.936, <i>p</i> = 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, <i>p</i> = 0.017), which was consistent with the results in UK Biobank and the combined OR was 0.747 (95% CI, 0.584–0.955, <i>p</i> = 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.https://www.mdpi.com/2072-6643/14/15/3237antioxidantascorbateretinoldigestive system cancersmendelian randomization |
| spellingShingle | Xuening Zhang Hao Zhao Jinyu Man Xiaolin Yin Tongchao Zhang Xiaorong Yang Ming Lu Investigating Causal Associations of Diet-Derived Circulating Antioxidants with the Risk of Digestive System Cancers: A Mendelian Randomization Study Nutrients antioxidant ascorbate retinol digestive system cancers mendelian randomization |
| 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 | antioxidant ascorbate retinol digestive system cancers mendelian randomization |
| url | https://www.mdpi.com/2072-6643/14/15/3237 |
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