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Blood pressure and bladder cancer risk in men by use of survival analysis and in interaction with NAT2 genotype, and by Mendelian randomization analysis

Teleka, Stanley LU ; Hindy, George LU ; Drake, Isabel LU ; Poveda, Alaitz LU orcid ; Melander, Olle LU orcid ; Liedberg, Fredrik LU ; Orho-Melander, Marju LU and Stocks, Tanja LU (2020) In PLoS ONE 15(11 November).
Abstract

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... (More)

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.

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author
; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
PLoS ONE
volume
15
issue
11 November
article number
e0241711
publisher
Public Library of Science (PLoS)
external identifiers
  • scopus:85096816265
  • pmid:33237904
ISSN
1932-6203
DOI
10.1371/journal.pone.0241711
project
Metabolic factors, smoking and genetic variation in relation to bladder cancer risk and prognosis
language
English
LU publication?
yes
id
55d9234e-dd3e-4f59-abe4-5b5e3325e171
date added to LUP
2020-12-11 12:43:19
date last changed
2024-05-15 23:39:03
@article{55d9234e-dd3e-4f59-abe4-5b5e3325e171,
  abstract     = {{<p>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.</p>}},
  author       = {{Teleka, Stanley and Hindy, George and Drake, Isabel and Poveda, Alaitz and Melander, Olle and Liedberg, Fredrik and Orho-Melander, Marju and Stocks, Tanja}},
  issn         = {{1932-6203}},
  language     = {{eng}},
  number       = {{11 November}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  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}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0241711}},
  doi          = {{10.1371/journal.pone.0241711}},
  volume       = {{15}},
  year         = {{2020}},
}