Key result
Genetically predicted higher systolic blood pressure was not associated with an increased risk of total cancer (OR 0.98, 95% CI 0.89-1.07 per standard deviation increase).
Why the study?
Observational studies link higher blood pressure to cancer, but Mendelian randomization was needed to obtain less confounded estimates.
Does genetically predicted higher blood pressure increase the risk of total and site-specific cancers in individuals of European ancestry?
Observational (n=405,243)
Mendelian randomization
Yes
Does genetically predicted higher blood pressure increase the risk of total and site-specific cancers in individuals of European ancestry?
Genetically predicted blood pressure is not associated with an increased risk of cancer, suggesting that previous observational links may be due to confounding.
Answers are grounded in this paper and cite their sources.
MR evidence indicates BP is not causally linked to most cancers; challenges prior observational associations and leaves causal effects open for melanoma.
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.
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Chan et al. (2021) conducted an observational in Cancer (n=405,243). Systolic blood pressure (per 1-SD increment) vs. Unexposed/reference (lower blood pressure) was evaluated on Total cancer (OR 0.98, 95% CI 0.89-1.07, p=0.619). Genetically predicted higher systolic blood pressure was not associated with an increased risk of total cancer (OR 0.98, 95% CI 0.89-1.07 per standard deviation increase).
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