Predicting the effect of statins on cancer risk using genetic variants from a Mendelian randomization study in the UK Biobank
Figures
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig1-v1.tif/full/617,/0/default.jpg)
Power calculations for polygenic and gene-specific analyses, displaying the Mendelian randomization estimate that can be detected with 80% power assuming a sample size of 367,703 individuals for site-specific cancers.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with 95% confidence interval per one standard deviation increase in lipid fraction) for variants in gene regions representing targets of lipid-lowering treatments.
Estimates are scaled to a one standard deviation increase in LDL-cholesterol for the HMGCR, PCSK9, LDLR, and NPC1L1 regions, and a one standard deviation increase in triglycerides for the APOC3 and LPL regions. A: associations with overall cancer for each gene region in turn. B: associations with site-specific cancers for variants in the HMGCR gene region.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp1-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with 95% confidence interval per one standard deviation increase in LDL-cholesterol) for variants in the PCSK9 gene region.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp2-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with95%confidence interval per one standard deviation increase in LDL-cholesterol) for variants in theLDLRgene region.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp3-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with 95% confidence interval per one standard deviation increase in LDL-cholesterol) for variants in theNPC1L1gene region.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp4-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with 95% confidence interval per one standard deviation increase in LDL-cholesterol) for variants in theAPOC3gene region.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp5-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with 95% confidence interval per one standard deviation increase in LDL-cholesterol) for variants in theLPLgene region.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp6-v1.tif/full/617,/0/default.jpg)
Genetic associations with LDL-cholesterol (standard deviation units) plotted against genetic associations with overall cancer (log odds ratios) for six variants in the HMGCR gene region.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp7-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with 95% confidence interval per one standard deviation increase in LDL-cholesterol) for variants in the HMGCR gene region excluding self-reported outcomes.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig2-figsupp8-v1.tif/full/617,/0/default.jpg)
Gene-specific Mendelian randomization estimates (odds ratio with 95% confidence interval per one standard deviation increase in LDL-cholesterol) for variants in the HMGCR gene region excluding those with a cancer diagnosis other than site-specific cancer under analysis.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig3-v1.tif/full/617,/0/default.jpg)
Multivariable Mendelian randomization estimates for HDL-cholesterol, LDL-cholesterol, and triglycerides (odds ratio with 95% confidence interval per one standard deviation increase in lipid fraction) from polygenic analyses including all lipid-associated variants.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig3-figsupp1-v1.tif/full/617,/0/default.jpg)
Multivariable Mendelian randomization estimates for HDL-cholesterol, LDL-cholesterol, and triglycerides (odds ratio with 95% confidence interval per one standard deviation increase in lipid fraction) from polygenic analyses including all lipid-associated variants excluding self-reported outcomes.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig3-figsupp2-v1.tif/full/617,/0/default.jpg)
Multivariable Mendelian randomization estimates for HDL-cholesterol, LDL-cholesterol, and triglycerides (odds ratio with 95% confidence interval per one standard deviation increase in lipid fraction) from polygenic analyses including all lipid-associated variants excluding those with a cancer diagnosis other than the site-specific cancer under analysis.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig4-v1.tif/full/617,/0/default.jpg)
Univariable Mendelian randomization estimates for total cholesterol (odds ratio with 95% confidence interval per one standard deviation increase in lipid fraction) from polygenic analyses including all lipid-associated variants.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig4-figsupp1-v1.tif/full/617,/0/default.jpg)
Univariable Mendelian randomization estimates for total cholesterol (odds ratio with 95% confidence interval per one standard deviation increase in lipid fraction) from polygenic analyses including all lipid-associated variants excluding self-reported outcomes.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig4-figsupp2-v1.tif/full/617,/0/default.jpg)
Univariable Mendelian randomization estimates for total cholesterol (odds ratio with 95% confidence interval per one standard deviation increase in lipid fraction) from polygenic analyses including all lipid-associated variants excluding those with a cancer diagnosis other than the site-specific cancer under analysis.
![](https://iiif.elifesciences.org/lax/57191%2Felife-57191-fig4-figsupp3-v1.tif/full/617,/0/default.jpg)
Scatterplot to assess heterogeneity of genetic associations with total cholesterol (horizontal axis, standard deviation units) against genetic associations with overall cancer (vertical axis, log odds ratios).
Error bars represent 95% confidence intervals. Solid diagonal line represents the inverse-variance weighted estimate.
Tables
Baseline characteristics of the UK Biobank participants included in this study and the numbers of outcome events.
Characteristic or cancer site/type | Mean (SD) or N (%)† |
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Sample size | 367,703 (100) |
Female | 198,904 (54.1) |
Age at baseline | 57.2 (8.1) |
Body mass index | 27.3 (4.8) |
Systolic blood pressure | 137.6 (18.6) |
Diastolic blood pressure | 82.0 (10.1) |
Smoking status (current/ex/ never)* | 37,866 (10.3)/185,704 (50.5)/143,777 (39.1) |
Alcohol status (current/ex/ never)* | 342,797 (93.2)/12,732 (3.5)/11,646 (3.2) |
History of type 2 diabetes | 15,834 (4.3) |
Overall cancer | 75,037 (20.4) |
Breast | 13,666 (6.9) |
Prostate | 7872 (4.7) |
Lung | 2838 (0.8) |
Bowel | 5486 (1.5) |
Melanoma | 4869 (1.3) |
Non-Hodgkin’s lymphoma | 2296 (0.6) |
Kidney | 1310 (0.4) |
Head/neck | 1615 (0.4) |
Brain | 810 (0.2) |
Bladder | 2588 (0.7) |
Pancreas | 1264 (0.3) |
Uterus | 1931 (1.0) |
Leukaemia | 1403 (0.4) |
Esophagus | 843 (0.2) |
Ovaries | 1520 (0.8) |
Gastric | 736 (0.2) |
Liver | 324 (0.1) |
Myeloma | 656 (0.2) |
Thyroid | 375 (0.1) |
Biliary | 387 (0.1) |
Cervix | 1928 (1.0) |
Testes | 735 (0.4) |
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*Excluding 356 participants with smoking status absent and 528 participants with alcohol consumption status absent.
†For sex-specific cancers, this is the percentage of individuals of the relevant sex.
Additional files
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Source code 1
R files for performing Mendelian randomization analyses.
- https://cdn.elifesciences.org/articles/57191/elife-57191-code1-v1.zip
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Source data 1
Summarized genetic associations with cancer outcomes estimated in UK Biobank.
- https://cdn.elifesciences.org/articles/57191/elife-57191-data1-v1.zip
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Supplementary file 1
Supplementary tables 1-8.
- https://cdn.elifesciences.org/articles/57191/elife-57191-supp1-v1.docx
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Transparent reporting form
- https://cdn.elifesciences.org/articles/57191/elife-57191-transrepform-v1.docx