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Olle Melander

Principal investigator

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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

Author

  • Stanley Teleka
  • George Hindy
  • Isabel Drake
  • Alaitz Poveda
  • Olle Melander
  • Fredrik Liedberg
  • Marju Orho-Melander
  • Tanja Stocks

Summary, in English

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.

Department/s

  • LUCC - Lund University Cancer Centre
  • Register-based epidemiology
  • EpiHealth: Epidemiology for Health
  • EXODIAB: Excellence in Diabetes Research in Sweden
  • Diabetes - Cardiovascular Disease
  • Genetic and Molecular Epidemiology
  • Cardiovascular Research - Hypertension
  • Urology - urothelial cancer, Malmö

Publishing year

2020

Language

English

Publication/Series

PLoS ONE

Volume

15

Issue

11 November

Document type

Journal article

Publisher

Public Library of Science

Topic

  • Cancer and Oncology
  • Medical Genetics

Status

Published

Project

  • Metabolic factors, smoking and genetic variation in relation to bladder cancer risk and prognosis

Research group

  • Register-based epidemiology
  • Diabetes - Cardiovascular Disease
  • Genetic and Molecular Epidemiology
  • Cardiovascular Research - Hypertension
  • Urology - urothelial cancer, Malmö

ISBN/ISSN/Other

  • ISSN: 1932-6203