Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis.
The association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an...
Main Authors: | , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Public Library of Science (PLoS)
2020-01-01
|
Series: | PLoS ONE |
Online Access: | https://doi.org/10.1371/journal.pone.0241711 |
id |
doaj-6a4df0db12c544e08d2b8e4d4645fbc0 |
---|---|
record_format |
Article |
spelling |
doaj-6a4df0db12c544e08d2b8e4d4645fbc02021-03-04T13:05:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032020-01-011511e024171110.1371/journal.pone.0241711Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis.Stanley TelekaGeorge HindyIsabel DrakeAlaitz PovedaOlle MelanderFredrik LiedbergMarju Orho-MelanderTanja StocksThe association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an attempt to disconnect the association from smoking. We additionally investigated the interaction between BP and N-acetyltransferase-2 (NAT2) rs1495741, an established BC genetic risk variant, in the association. Populations consisting of 188,167 men with 502 incident BC's in the UK-biobank and 27,107 men with 928 incident BC's in two Swedish cohorts were used for the analysis. We found a positive association between systolic BP and BC risk in Cox-regression survival analysis in the Swedish cohorts, (hazard ratio [HR] per standard deviation [SD]: 1.14 [95% confidence interval 1.05-1.22]) and MR analysis (odds ratio per SD: 2-stage least-square regression, 7.70 [1.92-30.9]; inverse-variance weighted estimate, 3.43 [1.12-10.5]), and no associations in the UK-biobank (HR systolic BP: 0.93 [0.85-1.02]; MR OR: 1.24 [0.35-4.40] and 1.37 [0.43-4.37], respectively). BP levels were positively associated with muscle-invasive BC (MIBC) (HRs: systolic BP, 1.32 [1.09-1.59]; diastolic BP, 1.27 [1.04-1.55]), but not with non-muscle invasive BC, which could be analyzed in the Swedish cohorts only. There was no interaction between BP and NAT2 in relation to BC on the additive or multiplicative scale. These results suggest that BP might be related to BC, more particularly MIBC. There was no evidence to support interaction between BP and NAT2 in relation to BC in our study.https://doi.org/10.1371/journal.pone.0241711 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stanley Teleka George Hindy Isabel Drake Alaitz Poveda Olle Melander Fredrik Liedberg Marju Orho-Melander Tanja Stocks |
spellingShingle |
Stanley Teleka George Hindy Isabel Drake Alaitz Poveda Olle Melander Fredrik Liedberg Marju Orho-Melander Tanja Stocks Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis. PLoS ONE |
author_facet |
Stanley Teleka George Hindy Isabel Drake Alaitz Poveda Olle Melander Fredrik Liedberg Marju Orho-Melander Tanja Stocks |
author_sort |
Stanley Teleka |
title |
Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis. |
title_short |
Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis. |
title_full |
Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis. |
title_fullStr |
Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis. |
title_full_unstemmed |
Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis. |
title_sort |
blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with nat2 genotype, and by mendelian randomization analysis. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2020-01-01 |
description |
The association between blood pressure (BP) and bladder cancer (BC) risk remains unclear with confounding by smoking being of particular concern. We investigated the association between BP and BC risk among men using conventional survival-analysis, and by Mendelian Randomization (MR) analysis in an attempt to disconnect the association from smoking. We additionally investigated the interaction between BP and N-acetyltransferase-2 (NAT2) rs1495741, an established BC genetic risk variant, in the association. Populations consisting of 188,167 men with 502 incident BC's in the UK-biobank and 27,107 men with 928 incident BC's in two Swedish cohorts were used for the analysis. We found a positive association between systolic BP and BC risk in Cox-regression survival analysis in the Swedish cohorts, (hazard ratio [HR] per standard deviation [SD]: 1.14 [95% confidence interval 1.05-1.22]) and MR analysis (odds ratio per SD: 2-stage least-square regression, 7.70 [1.92-30.9]; inverse-variance weighted estimate, 3.43 [1.12-10.5]), and no associations in the UK-biobank (HR systolic BP: 0.93 [0.85-1.02]; MR OR: 1.24 [0.35-4.40] and 1.37 [0.43-4.37], respectively). BP levels were positively associated with muscle-invasive BC (MIBC) (HRs: systolic BP, 1.32 [1.09-1.59]; diastolic BP, 1.27 [1.04-1.55]), but not with non-muscle invasive BC, which could be analyzed in the Swedish cohorts only. There was no interaction between BP and NAT2 in relation to BC on the additive or multiplicative scale. These results suggest that BP might be related to BC, more particularly MIBC. There was no evidence to support interaction between BP and NAT2 in relation to BC in our study. |
url |
https://doi.org/10.1371/journal.pone.0241711 |
work_keys_str_mv |
AT stanleyteleka bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis AT georgehindy bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis AT isabeldrake bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis AT alaitzpoveda bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis AT ollemelander bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis AT fredrikliedberg bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis AT marjuorhomelander bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis AT tanjastocks bloodpressureandbladdercancerriskinmenbyuseofsurvivalanalysisandininteractionwithnat2genotypeandbymendelianrandomizationanalysis |
_version_ |
1714800721151393792 |