Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study
BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by mea...
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| Autor*in: |
Zhang Cheng [verfasserIn] Fangdie Ye [verfasserIn] Yingchun Liang [verfasserIn] Chenyang Xu [verfasserIn] Zheyu Zhang [verfasserIn] Yuxi Ou [verfasserIn] Xinan Chen [verfasserIn] Xiyu Dai [verfasserIn] Zezhong Mou [verfasserIn] Weijian Li [verfasserIn] Yiling Chen [verfasserIn] Quan Zhou [verfasserIn] Lujia Zou [verfasserIn] Shanhua Mao [verfasserIn] Haowen Jiang [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2023 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
In: Frontiers in Nutrition - Frontiers Media S.A., 2014, 10(2023) |
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| Übergeordnetes Werk: |
volume:10 ; year:2023 |
| Links: |
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| DOI / URN: |
10.3389/fnut.2023.992608 |
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| Katalog-ID: |
DOAJ098779591 |
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| 520 | |a BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. | ||
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| 700 | 0 | |a Yingchun Liang |e verfasserin |4 aut | |
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| 700 | 0 | |a Chenyang Xu |e verfasserin |4 aut | |
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10.3389/fnut.2023.992608 doi (DE-627)DOAJ098779591 (DE-599)DOAJ88e8db95706445f3aa4ad3f736ea92e9 DE-627 ger DE-627 rakwb eng TX341-641 Zhang Cheng verfasserin aut Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. blood lipids lipid-regulatory medications bladder cancer Mendelian randomization UK Biobank FinnGen Nutrition. Foods and food supply Zhang Cheng verfasserin aut Fangdie Ye verfasserin aut Fangdie Ye verfasserin aut Yingchun Liang verfasserin aut Yingchun Liang verfasserin aut Chenyang Xu verfasserin aut Chenyang Xu verfasserin aut Zheyu Zhang verfasserin aut Zheyu Zhang verfasserin aut Yuxi Ou verfasserin aut Yuxi Ou verfasserin aut Xinan Chen verfasserin aut Xinan Chen verfasserin aut Xiyu Dai verfasserin aut Xiyu Dai verfasserin aut Zezhong Mou verfasserin aut Zezhong Mou verfasserin aut Weijian Li verfasserin aut Weijian Li verfasserin aut Yiling Chen verfasserin aut Yiling Chen verfasserin aut Quan Zhou verfasserin aut Quan Zhou verfasserin aut Lujia Zou verfasserin aut Lujia Zou verfasserin aut Shanhua Mao verfasserin aut Shanhua Mao verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut In Frontiers in Nutrition Frontiers Media S.A., 2014 10(2023) (DE-627)790231158 (DE-600)2776676-7 2296861X nnns volume:10 year:2023 https://doi.org/10.3389/fnut.2023.992608 kostenfrei https://doaj.org/article/88e8db95706445f3aa4ad3f736ea92e9 kostenfrei https://www.frontiersin.org/articles/10.3389/fnut.2023.992608/full kostenfrei https://doaj.org/toc/2296-861X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 |
| spelling |
10.3389/fnut.2023.992608 doi (DE-627)DOAJ098779591 (DE-599)DOAJ88e8db95706445f3aa4ad3f736ea92e9 DE-627 ger DE-627 rakwb eng TX341-641 Zhang Cheng verfasserin aut Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. blood lipids lipid-regulatory medications bladder cancer Mendelian randomization UK Biobank FinnGen Nutrition. Foods and food supply Zhang Cheng verfasserin aut Fangdie Ye verfasserin aut Fangdie Ye verfasserin aut Yingchun Liang verfasserin aut Yingchun Liang verfasserin aut Chenyang Xu verfasserin aut Chenyang Xu verfasserin aut Zheyu Zhang verfasserin aut Zheyu Zhang verfasserin aut Yuxi Ou verfasserin aut Yuxi Ou verfasserin aut Xinan Chen verfasserin aut Xinan Chen verfasserin aut Xiyu Dai verfasserin aut Xiyu Dai verfasserin aut Zezhong Mou verfasserin aut Zezhong Mou verfasserin aut Weijian Li verfasserin aut Weijian Li verfasserin aut Yiling Chen verfasserin aut Yiling Chen verfasserin aut Quan Zhou verfasserin aut Quan Zhou verfasserin aut Lujia Zou verfasserin aut Lujia Zou verfasserin aut Shanhua Mao verfasserin aut Shanhua Mao verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut In Frontiers in Nutrition Frontiers Media S.A., 2014 10(2023) (DE-627)790231158 (DE-600)2776676-7 2296861X nnns volume:10 year:2023 https://doi.org/10.3389/fnut.2023.992608 kostenfrei https://doaj.org/article/88e8db95706445f3aa4ad3f736ea92e9 kostenfrei https://www.frontiersin.org/articles/10.3389/fnut.2023.992608/full kostenfrei https://doaj.org/toc/2296-861X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 |
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10.3389/fnut.2023.992608 doi (DE-627)DOAJ098779591 (DE-599)DOAJ88e8db95706445f3aa4ad3f736ea92e9 DE-627 ger DE-627 rakwb eng TX341-641 Zhang Cheng verfasserin aut Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. blood lipids lipid-regulatory medications bladder cancer Mendelian randomization UK Biobank FinnGen Nutrition. Foods and food supply Zhang Cheng verfasserin aut Fangdie Ye verfasserin aut Fangdie Ye verfasserin aut Yingchun Liang verfasserin aut Yingchun Liang verfasserin aut Chenyang Xu verfasserin aut Chenyang Xu verfasserin aut Zheyu Zhang verfasserin aut Zheyu Zhang verfasserin aut Yuxi Ou verfasserin aut Yuxi Ou verfasserin aut Xinan Chen verfasserin aut Xinan Chen verfasserin aut Xiyu Dai verfasserin aut Xiyu Dai verfasserin aut Zezhong Mou verfasserin aut Zezhong Mou verfasserin aut Weijian Li verfasserin aut Weijian Li verfasserin aut Yiling Chen verfasserin aut Yiling Chen verfasserin aut Quan Zhou verfasserin aut Quan Zhou verfasserin aut Lujia Zou verfasserin aut Lujia Zou verfasserin aut Shanhua Mao verfasserin aut Shanhua Mao verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut In Frontiers in Nutrition Frontiers Media S.A., 2014 10(2023) (DE-627)790231158 (DE-600)2776676-7 2296861X nnns volume:10 year:2023 https://doi.org/10.3389/fnut.2023.992608 kostenfrei https://doaj.org/article/88e8db95706445f3aa4ad3f736ea92e9 kostenfrei https://www.frontiersin.org/articles/10.3389/fnut.2023.992608/full kostenfrei https://doaj.org/toc/2296-861X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 |
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10.3389/fnut.2023.992608 doi (DE-627)DOAJ098779591 (DE-599)DOAJ88e8db95706445f3aa4ad3f736ea92e9 DE-627 ger DE-627 rakwb eng TX341-641 Zhang Cheng verfasserin aut Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. blood lipids lipid-regulatory medications bladder cancer Mendelian randomization UK Biobank FinnGen Nutrition. Foods and food supply Zhang Cheng verfasserin aut Fangdie Ye verfasserin aut Fangdie Ye verfasserin aut Yingchun Liang verfasserin aut Yingchun Liang verfasserin aut Chenyang Xu verfasserin aut Chenyang Xu verfasserin aut Zheyu Zhang verfasserin aut Zheyu Zhang verfasserin aut Yuxi Ou verfasserin aut Yuxi Ou verfasserin aut Xinan Chen verfasserin aut Xinan Chen verfasserin aut Xiyu Dai verfasserin aut Xiyu Dai verfasserin aut Zezhong Mou verfasserin aut Zezhong Mou verfasserin aut Weijian Li verfasserin aut Weijian Li verfasserin aut Yiling Chen verfasserin aut Yiling Chen verfasserin aut Quan Zhou verfasserin aut Quan Zhou verfasserin aut Lujia Zou verfasserin aut Lujia Zou verfasserin aut Shanhua Mao verfasserin aut Shanhua Mao verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut In Frontiers in Nutrition Frontiers Media S.A., 2014 10(2023) (DE-627)790231158 (DE-600)2776676-7 2296861X nnns volume:10 year:2023 https://doi.org/10.3389/fnut.2023.992608 kostenfrei https://doaj.org/article/88e8db95706445f3aa4ad3f736ea92e9 kostenfrei https://www.frontiersin.org/articles/10.3389/fnut.2023.992608/full kostenfrei https://doaj.org/toc/2296-861X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 |
| allfieldsSound |
10.3389/fnut.2023.992608 doi (DE-627)DOAJ098779591 (DE-599)DOAJ88e8db95706445f3aa4ad3f736ea92e9 DE-627 ger DE-627 rakwb eng TX341-641 Zhang Cheng verfasserin aut Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study 2023 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. blood lipids lipid-regulatory medications bladder cancer Mendelian randomization UK Biobank FinnGen Nutrition. Foods and food supply Zhang Cheng verfasserin aut Fangdie Ye verfasserin aut Fangdie Ye verfasserin aut Yingchun Liang verfasserin aut Yingchun Liang verfasserin aut Chenyang Xu verfasserin aut Chenyang Xu verfasserin aut Zheyu Zhang verfasserin aut Zheyu Zhang verfasserin aut Yuxi Ou verfasserin aut Yuxi Ou verfasserin aut Xinan Chen verfasserin aut Xinan Chen verfasserin aut Xiyu Dai verfasserin aut Xiyu Dai verfasserin aut Zezhong Mou verfasserin aut Zezhong Mou verfasserin aut Weijian Li verfasserin aut Weijian Li verfasserin aut Yiling Chen verfasserin aut Yiling Chen verfasserin aut Quan Zhou verfasserin aut Quan Zhou verfasserin aut Lujia Zou verfasserin aut Lujia Zou verfasserin aut Shanhua Mao verfasserin aut Shanhua Mao verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut Haowen Jiang verfasserin aut In Frontiers in Nutrition Frontiers Media S.A., 2014 10(2023) (DE-627)790231158 (DE-600)2776676-7 2296861X nnns volume:10 year:2023 https://doi.org/10.3389/fnut.2023.992608 kostenfrei https://doaj.org/article/88e8db95706445f3aa4ad3f736ea92e9 kostenfrei https://www.frontiersin.org/articles/10.3389/fnut.2023.992608/full kostenfrei https://doaj.org/toc/2296-861X Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ GBV_ILN_11 GBV_ILN_20 GBV_ILN_22 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2003 GBV_ILN_2014 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4367 GBV_ILN_4700 AR 10 2023 |
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Zhang Cheng @@aut@@ Fangdie Ye @@aut@@ Yingchun Liang @@aut@@ Chenyang Xu @@aut@@ Zheyu Zhang @@aut@@ Yuxi Ou @@aut@@ Xinan Chen @@aut@@ Xiyu Dai @@aut@@ Zezhong Mou @@aut@@ Weijian Li @@aut@@ Yiling Chen @@aut@@ Quan Zhou @@aut@@ Lujia Zou @@aut@@ Shanhua Mao @@aut@@ Haowen Jiang @@aut@@ |
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We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p &gt; 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. 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Zhang Cheng Fangdie Ye Yingchun Liang Chenyang Xu Zheyu Zhang Yuxi Ou Xinan Chen Xiyu Dai Zezhong Mou Weijian Li Yiling Chen Quan Zhou Lujia Zou Shanhua Mao Haowen Jiang |
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Blood lipids, lipid-regulatory medications, and risk of bladder cancer: a Mendelian randomization study |
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BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. |
| abstractGer |
BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. |
| abstract_unstemmed |
BackgroundThe influences of blood lipids and lipid-regulatory medications on the risk of bladder cancer have long been suspected, and previous findings remain controversial. We aimed to assess the causality between blood lipids or lipid-regulatory medications and bladder cancer susceptibility by means of a comprehensive Mendelian Randomization (MR) study.MethodsGenetic proxies from genome-wide association studies (GWAS) of four blood lipid traits and lipid-lowering variants in genes encoding the targets of lipid-regulatory medications were employed. The largest ever GWAS data of blood lipids and bladder cancer involving up to 440,546 and 205,771 individuals of European ancestry were extracted from UK Biobank and FinnGen Project Round 6, respectively. A two-sample bidirectional MR study was performed using the inverse variance weighted as the main method. The heterogeneity, horizontal pleiotropy, MR Steiger, and leave-one-out analyses were also conducted as sensitivity tests.ResultsThere was indicative evidence that genetically predicted low-density lipoprotein cholesterol (LDL-C) affected bladder cancer susceptibility based on 146 single nucleotide polymorphisms (SNPs) with an odds ratio (OR) of 0.776 (95% confidence interval [CI] = 0.625–0.965, p = 0.022). However, this result became non-significant after two SNPs that possibly drove the effect were removed as demonstrated by leave-one-out analysis. The reversed MR analysis suggested that bladder cancer could not affect serum lipid levels. No causal relationship was found between the lipid-lowering effect of lipid-regulatory medications (fibrates, probucol, statins, ezetimibe, proprotein convertase subtilisin/kexin type 9 [PCSK9] inhibitors, and evinacumab) and the risk of bladder cancer. No heterogeneity or pleiotropy was found (all p > 0.05).ConclusionThis MR study revealed for the first time, using the most recent and comprehensive GWAS data to date, that genetically predicted total cholesterol (TC) and the lipid-lowering effect of lipid-regulatory medications had no causal association with bladder cancer susceptibility. We also verified claims from early studies that low-density lipoprotein cholesterol (HDL-C), LDL-C, and triglyceride (TG) are not related to bladder cancer susceptibility either. The current study indicated that lipid metabolism may not be as important in the tumorigenesis of bladder cancer as previously believed. |
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