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Blood pressure and risk of cancer: a Mendelian randomization study
BACKGROUND: Previous large observational cohort studies showed higher blood pressure (BP) positively associated with cancer. We used Mendelian randomization (MR) to obtain less confounded estimates of BP on total and site-specific cancers. METHODS: We applied replicated genetic instruments for systo...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675492/ https://www.ncbi.nlm.nih.gov/pubmed/34915881 http://dx.doi.org/10.1186/s12885-021-09067-x |
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author | Chan, Io Ieong Kwok, Man Ki Schooling, C. Mary |
author_facet | Chan, Io Ieong Kwok, Man Ki Schooling, C. Mary |
author_sort | Chan, Io Ieong |
collection | PubMed |
description | BACKGROUND: Previous large observational cohort studies showed higher blood pressure (BP) positively associated with cancer. We used Mendelian randomization (MR) to obtain less confounded estimates of BP on total and site-specific cancers. METHODS: We applied replicated genetic instruments for systolic and diastolic BP to summary genetic associations with total cancer (37387 cases, 367856 non-cases) from the UK Biobank, and 17 site-specific cancers (663–17881 cases) from a meta-analysis of the UK Biobank and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging. We used inverse-variance weighting with multiplicative random effects as the main analysis, and sensitivity analyses including the weighted median, MR-Egger and multivariable MR adjusted for body mass index and for smoking. For validation, we included breast (Breast Cancer Association Consortium: 133384 cases, 113789 non-cases), prostate (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome Consortium: 79194 cases, 61112 non-cases) and lung (International Lung and Cancer Consortium: 10246 cases, 38295 non-cases) cancer from large consortia. We used asthma as a negative control outcome. RESULTS: Systolic and diastolic BP were unrelated to total cancer (OR 0.98 per standard deviation higher [95% confidence interval (CI) 0.89, 1.07] and OR 1.00 [95% CI 0.92, 1.08]) and to site-specific cancers after accounting for multiple testing, with consistent findings from consortia. BP was nominally associated with melanoma and possibly kidney cancer, and as expected, not associated with asthma. Sensitivity analyses using other MR methods gave similar results. CONCLUSIONS: In contrast to previous observational evidence, BP does not appear to be a risk factor for cancer, although an effect on melanoma and kidney cancer cannot be excluded. Other targets for cancer prevention might be more relevant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09067-x. |
format | Online Article Text |
id | pubmed-8675492 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-86754922021-12-20 Blood pressure and risk of cancer: a Mendelian randomization study Chan, Io Ieong Kwok, Man Ki Schooling, C. Mary BMC Cancer Research BACKGROUND: Previous large observational cohort studies showed higher blood pressure (BP) positively associated with cancer. We used Mendelian randomization (MR) to obtain less confounded estimates of BP on total and site-specific cancers. METHODS: We applied replicated genetic instruments for systolic and diastolic BP to summary genetic associations with total cancer (37387 cases, 367856 non-cases) from the UK Biobank, and 17 site-specific cancers (663–17881 cases) from a meta-analysis of the UK Biobank and the Kaiser Permanente Genetic Epidemiology Research on Adult Health and Aging. We used inverse-variance weighting with multiplicative random effects as the main analysis, and sensitivity analyses including the weighted median, MR-Egger and multivariable MR adjusted for body mass index and for smoking. For validation, we included breast (Breast Cancer Association Consortium: 133384 cases, 113789 non-cases), prostate (Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome Consortium: 79194 cases, 61112 non-cases) and lung (International Lung and Cancer Consortium: 10246 cases, 38295 non-cases) cancer from large consortia. We used asthma as a negative control outcome. RESULTS: Systolic and diastolic BP were unrelated to total cancer (OR 0.98 per standard deviation higher [95% confidence interval (CI) 0.89, 1.07] and OR 1.00 [95% CI 0.92, 1.08]) and to site-specific cancers after accounting for multiple testing, with consistent findings from consortia. BP was nominally associated with melanoma and possibly kidney cancer, and as expected, not associated with asthma. Sensitivity analyses using other MR methods gave similar results. CONCLUSIONS: In contrast to previous observational evidence, BP does not appear to be a risk factor for cancer, although an effect on melanoma and kidney cancer cannot be excluded. Other targets for cancer prevention might be more relevant. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12885-021-09067-x. BioMed Central 2021-12-16 /pmc/articles/PMC8675492/ /pubmed/34915881 http://dx.doi.org/10.1186/s12885-021-09067-x Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chan, Io Ieong Kwok, Man Ki Schooling, C. Mary Blood pressure and risk of cancer: a Mendelian randomization study |
title | Blood pressure and risk of cancer: a Mendelian randomization study |
title_full | Blood pressure and risk of cancer: a Mendelian randomization study |
title_fullStr | Blood pressure and risk of cancer: a Mendelian randomization study |
title_full_unstemmed | Blood pressure and risk of cancer: a Mendelian randomization study |
title_short | Blood pressure and risk of cancer: a Mendelian randomization study |
title_sort | blood pressure and risk of cancer: a mendelian randomization study |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8675492/ https://www.ncbi.nlm.nih.gov/pubmed/34915881 http://dx.doi.org/10.1186/s12885-021-09067-x |
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