Predicting the effect of statins on cancer risk using genetic variants from a Mendelian randomization study in the UK Biobank
Laboratory studies have suggested oncogenic roles of lipids, as well as anticarcinogenic effects of statins. Here we assess the potential effect of statin therapy on cancer risk using evidence from human genetics. We obtained associations of lipid-related genetic variants with the risk of overall an...
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| creator | Carter, Paul Vithayathil, Mathew Kar, Siddhartha Potluri, Rahul Mason, Amy M. Larsson, Susanna C. Burgess, Stephen |
| description | Laboratory studies have suggested oncogenic roles of lipids, as well as anticarcinogenic effects of statins. Here we assess the potential effect of statin therapy on cancer risk using evidence from human genetics. We obtained associations of lipid-related genetic variants with the risk of overall and 22 site-specific cancers for 367,703 individuals in the UK Biobank. In total, 75,037 individuals had a cancer event. Variants in the HMGCR gene region, which represent proxies for statin treatment, were associated with overall cancer risk (odds ratio [OR] per one standard deviation decrease in low-density lipoprotein [LDL] cholesterol 0.76, 95% confidence interval [CI] 0.65-0.88, p=0.0003) but variants in gene regions representing alternative lipid-lowering treatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not. Genetically predicted LDL-cholesterol was not associated with overall cancer risk (OR per standard deviation increase 1.01, 95% CI 0.98-1.05, p=0.50). Our results predict that statins reduce cancer risk but other lipidlowering treatments do not. This suggests that statins reduce cancer risk through a cholesterol independent pathway. |
| doi_str_mv | 10.7554/eLife.57191 |
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Here we assess the potential effect of statin therapy on cancer risk using evidence from human genetics. We obtained associations of lipid-related genetic variants with the risk of overall and 22 site-specific cancers for 367,703 individuals in the UK Biobank. In total, 75,037 individuals had a cancer event. Variants in the HMGCR gene region, which represent proxies for statin treatment, were associated with overall cancer risk (odds ratio [OR] per one standard deviation decrease in low-density lipoprotein [LDL] cholesterol 0.76, 95% confidence interval [CI] 0.65-0.88, p=0.0003) but variants in gene regions representing alternative lipid-lowering treatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not. Genetically predicted LDL-cholesterol was not associated with overall cancer risk (OR per standard deviation increase 1.01, 95% CI 0.98-1.05, p=0.50). Our results predict that statins reduce cancer risk but other lipidlowering treatments do not. 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Vithayathil, Mathew ; Kar, Siddhartha ; Potluri, Rahul ; Mason, Amy M. ; Larsson, Susanna C. ; Burgess, Stephen</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-135d63e96971697e6e5d400e9c53dfc9ea91a4cbce48c41c95f8a991e55181513</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Biological Specimen Banks</topic><topic>Biology</topic><topic>causal inference</topic><topic>Cell Biology</topic><topic>cholesterol</topic><topic>Chromosomes and Gene Expression</topic><topic>genetic epidemiology</topic><topic>Genetic Variation</topic><topic>Hydroxymethylglutaryl CoA Reductases - genetics</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects</topic><topic>Life Sciences & Biomedicine</topic><topic>Life Sciences & Biomedicine - Other Topics</topic><topic>lipids</topic><topic>Medicin och hälsovetenskap</topic><topic>Mendelian randomization</topic><topic>Mendelian Randomization Analysis</topic><topic>Neoplasms - chemically induced</topic><topic>Neoplasms - epidemiology</topic><topic>Prevalence</topic><topic>Risk Factors</topic><topic>Science & Technology</topic><topic>statins</topic><topic>United Kingdom - epidemiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Carter, Paul</creatorcontrib><creatorcontrib>Vithayathil, Mathew</creatorcontrib><creatorcontrib>Kar, Siddhartha</creatorcontrib><creatorcontrib>Potluri, Rahul</creatorcontrib><creatorcontrib>Mason, Amy M.</creatorcontrib><creatorcontrib>Larsson, Susanna C.</creatorcontrib><creatorcontrib>Burgess, Stephen</creatorcontrib><collection>Web of Science - Science Citation Index Expanded - 2020</collection><collection>Web of Science Core Collection</collection><collection>Science Citation Index Expanded</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>PubMed Central (Full Participant titles)</collection><collection>SWEPUB Uppsala universitet full text</collection><collection>SwePub</collection><collection>SwePub Articles</collection><collection>SWEPUB Freely available online</collection><collection>SWEPUB Uppsala universitet</collection><collection>SwePub Articles full text</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>eLife</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Carter, Paul</au><au>Vithayathil, Mathew</au><au>Kar, Siddhartha</au><au>Potluri, Rahul</au><au>Mason, Amy M.</au><au>Larsson, Susanna C.</au><au>Burgess, Stephen</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Predicting the effect of statins on cancer risk using genetic variants from a Mendelian randomization study in the UK Biobank</atitle><jtitle>eLife</jtitle><stitle>ELIFE</stitle><addtitle>Elife</addtitle><date>2020-10-13</date><risdate>2020</risdate><volume>9</volume><artnum>57191</artnum><issn>2050-084X</issn><eissn>2050-084X</eissn><abstract>Laboratory studies have suggested oncogenic roles of lipids, as well as anticarcinogenic effects of statins. Here we assess the potential effect of statin therapy on cancer risk using evidence from human genetics. We obtained associations of lipid-related genetic variants with the risk of overall and 22 site-specific cancers for 367,703 individuals in the UK Biobank. In total, 75,037 individuals had a cancer event. Variants in the HMGCR gene region, which represent proxies for statin treatment, were associated with overall cancer risk (odds ratio [OR] per one standard deviation decrease in low-density lipoprotein [LDL] cholesterol 0.76, 95% confidence interval [CI] 0.65-0.88, p=0.0003) but variants in gene regions representing alternative lipid-lowering treatment targets (PCSK9, LDLR, NPC1L1, APOC3, LPL) were not. Genetically predicted LDL-cholesterol was not associated with overall cancer risk (OR per standard deviation increase 1.01, 95% CI 0.98-1.05, p=0.50). Our results predict that statins reduce cancer risk but other lipidlowering treatments do not. 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| subjects | Biological Specimen Banks Biology causal inference Cell Biology cholesterol Chromosomes and Gene Expression genetic epidemiology Genetic Variation Hydroxymethylglutaryl CoA Reductases - genetics Hydroxymethylglutaryl-CoA Reductase Inhibitors - adverse effects Life Sciences & Biomedicine Life Sciences & Biomedicine - Other Topics lipids Medicin och hälsovetenskap Mendelian randomization Mendelian Randomization Analysis Neoplasms - chemically induced Neoplasms - epidemiology Prevalence Risk Factors Science & Technology statins United Kingdom - epidemiology |
| title | Predicting the effect of statins on cancer risk using genetic variants from a Mendelian randomization study in the UK Biobank |
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