| Title: | Association between circulating vitamin E and ten common cancers: evidence from large-scale Mendelian randomization analysis and a longitudinal cohort study |
| Journal: | BMC Medicine |
| Published: | 11 May 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/35538486/ |
| DOI: | https://doi.org/10.1186/s12916-022-02366-5 |
| URL: | https://bmcmedicine.biomedcentral.com/track/pdf/10.1186/s12916-022-02366-5 |
| Citations: | 33 (26 in last 2 years) as of 8 Aug 2024 |
Publication 12375
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Abstract
BackgroundThe 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.MethodsA 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.ResultsSpecific 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.ConclusionsThis 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.</p>
11 Keywords
- Breast Neoplasms
- Cohort Studies
- Female
- Genome-Wide Association Study
- Humans
- Likelihood Functions
- Longitudinal Studies
- Male
- Mendelian Randomization Analysis
- Polymorphism, Single Nucleotide
- Vitamin E
9 Authors
- Junyi Xin
- Xia Jiang
- Shuai Ben
- Qianyu Yuan
- Li Su
- Zhengdong Zhang
- David C. Christiani
- Mulong Du
- Meilin Wang
1 Application
| Application ID | Title |
|---|---|
| 45611 | Genome-wide cross-trait analysis for genetic architecture of pan-cancer by UK Biobank |
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