Causal relationships between risk of venous thromboembolism and 18 cancers: a bidirectional Mendelian randomization analysis

Naomi Cornish*, Philip Haycock, Hermann Brenner, Jane C Figueiredo, Tessel E Galesloot, Robert C Grant, Mattias Johansson, Daniela Mariosa, James McKay, Rish Pai, Andrew J Pellatt, N Jewel Samadder, Jianxin Shi, Florian Thibord, David-Alexandre Trégouët, Catherine Voegele, Chrissie Thirlwell, Andrew Mumford, Ryan Langdon, InterLymph Consortium, INVENT-MVP Consortium

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

Abstract

BACKGROUND: People with cancer experience high rates of venous thromboembolism (VTE). Risk of subsequent cancer is also increased in people experiencing their first VTE. The causal mechanisms underlying this association are not completely understood, and it is unknown whether VTE is itself a risk factor for cancer.

METHODS: We used data from large genome-wide association study meta-analyses to perform bidirectional Mendelian randomization analyses to estimate causal associations between genetic liability to VTE and risk of 18 different cancers.

RESULTS: We found no conclusive evidence that genetic liability to VTE was causally associated with an increased incidence of cancer, or vice versa. We observed an association between liability to VTE and pancreatic cancer risk [odds ratio for pancreatic cancer: 1.23 (95% confidence interval: 1.08-1.40) per log-odds increase in VTE risk, P = 0.002]. However, sensitivity analyses revealed this association was predominantly driven by a variant proxying non-O blood group, with inadequate evidence to suggest a causal relationship.

CONCLUSIONS: These findings do not support the hypothesis that genetic liability to VTE is a cause of cancer. Existing observational epidemiological associations between VTE and cancer are therefore more likely to be driven by pathophysiological changes which occur in the setting of active cancer and anti-cancer treatments. Further work is required to explore and synthesize evidence for these mechanisms.

Original languageEnglish
Article numberdyad170
Number of pages11
JournalInternational Journal of Epidemiology
Volume53
Issue number1
Early online date20 Dec 2023
DOIs
Publication statusPublished - 1 Feb 2024

Bibliographical note

Publisher Copyright: © The Author(s) 2023. Published by Oxford University Press on behalf of the International Epidemiological Association.

Structured keywords

  • ICEP

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