Association between circulating vitamin E and ten common cancers: evidence from large-scale Mendelian randomization analysis and a longitudinal cohort study

Abstract

Background The association between vitamin E and cancer risk has been widely investigated by observational studies, but the findings remain inconclusive. Here, we aimed to evaluate the causal effect of circulating vitamin E on the risk of ten common cancers, including bladder, breast, colorectal, esophagus, lung, oral and pharynx, ovarian, pancreatic, prostate, and kidney cancer. Methods A Mendelian randomization (MR) analytic framework was applied to data from a cancer-specific genome-wide association study (GWAS) comprising a total of 297,699 cancer cases and 304,736 controls of European ancestry. Three genetic instrumental variables associated with circulating vitamin E were selected. Summary statistic-based methods of inverse variance weighting (IVW) and likelihood-based approach, as well as the individual genotyping-based method of genetic risk score (GRS) were used. Multivariable IVW analysis was further performed to control for potential confounding effects. Furthermore, the UK Biobank cohort was used as external validation, supporting 355,543 European participants (incident cases ranged from 437 for ovarian cancer to 4882 for prostate cancer) for GRS-based estimation of circulating vitamin E, accompanied by a one-sample MR analysis of dietary vitamin E intake underlying the time-to-event analytic framework. Results Specific to cancer GWAS, we found that circulating vitamin E was significantly associated with increased bladder cancer risk (odds ratios [OR]IVW = 6.23, PIVW = 3.05×10-3) but decreased breast cancer risk (ORIVW = 0.68, PIVW = 8.19×10-3); however, the significance of breast cancer was dampened (Pmultivariable IVW > 0.05) in the subsequent multivariable MR analysis. In the validation stage of the UK Biobank cohort, we did not replicate convincing causal effects of genetically predicted circulating vitamin E concentrations and dietary vitamin E intake on the risk of ten cancers. Conclusions This large-scale population study upon data from cancer-specific GWAS and a longitudinal biobank cohort indicates plausible non-causal associations between circulating vitamin E and ten common cancers in the European populations. Further studies regarding ancestral diversity are warranted to validate such causal associations.

Relação Entre Vitamina E Plasmática E Os Grupos De Risco De Câncer De Próstata Com Indicação De Radioterapia Radical

“…A média dos níveis séricos de Vitamina E no Grupo A foi de 2,09 mg/dL (0,7-5,9 / IC95% 1,26-2,93 / DP ± 1,57), no Grupo B foi de 1,31 mg/dL (0,6-2,0 / IC95% 1,15-1,46 / DP ± 0,44) e no Grupo C foi de 0,8 mg/dL (0,5-1,0 / IC95% 0,69-0,90 / DP ± 0,19), Gráfico 1, com diferença estatisticamente significante (p < 0,001). A vitamina E é um grupo de nutrientes antioxidantes solúveis em gordura que consiste em oito isoformas naturais (Xin et al, 2022). Demonstrou-se que o estresse oxidativo está envolvido na patogênese de múltiplas doenças, especialmente para o câncer.…”

“…Demonstrou-se que o estresse oxidativo está envolvido na patogênese de múltiplas doenças, especialmente para o câncer. Estresse oxidativo pode levar a reação em cadeia de radicais livres causando peroxidação lipídica, mas a vitamina E desempenha um papel vital na quebra da reação em cadeia de radicais livres, evitando peroxidação lipídica e proteção da membrana biológica (Xin et al, 2022) média Vit E…”

Investigating Causal Associations of Circulating Micronutrients Concentrations with the Risk of Lung Cancer: A Mendelian Randomization Study

“…The preliminary catalogue includes 20 nutrients: beta carotene, calcium, copper, folate, iron, lycopene, magnesium, potassium, phosphorus, retinol, sodium, selenium, zinc, and vitamins B1, B2, B6, B12, C, D, and E [ 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 ]. We exclude iron and vitamins C, D, E, and B12 because the causal relationship between these circulating nutrient concentrations and LC risk has been thoroughly analyzed [ 30 , 31 , 32 , 33 , 34 ]. We further searched the genome-wide association studies (GWAS) catalogue ( (accessed on 4 August 2022)) and Pubmed for published GWAS on circulating micronutrient concentrations in European populations.…”

Vitamin E and Non-Communicable Diseases: A Review

“…Xin et al [ 67 ] investigated the relationship between vitamin E circulating levels and incidence of ten cancers. For breast cancer, they found that vitamin E levels were associated with a reduced breast cancer risk, but due to the low statistical significance of the result, the authors reported that it was not possible to establish a causal relationship between the two factors.…”