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Open Access 01-12-2023 | Colorectal Cancer | Research

Association between diverticular disease and colorectal cancer: a bidirectional mendelian randomization study

Authors: Yanxi Zhang, Han Zhang, Jinghan Zhu, Yazhou He, Peng Wang, Doudou Li, Xiaozhuan Liu, Wen Jin, Junxi Zhang, Chuan Xu, Zengli Yu, Xin Zhao, Lingling Cui

Published in: BMC Cancer | Issue 1/2023

Abstract

Background:

Diverticular disease has been inconsistently associated with colorectal cancer risk. We conducted a bidirectional Mendelian randomization study to assess this association.

Methods:

Forty-three and seventy single-nucleotide polymorphisms associated with diverticular disease and colorectal cancer at the genome-wide significance level (p < 5 × 10^− 8) were selected as instrumental variables from large-scale genome-wide association studies of European descent, respectively. Summary-level data for colon cancer, rectum cancer, and colorectal cancer were obtained from genome-wide association analyses of the FinnGen consortium and the UK Biobank study. Summary-level data for diverticular disease was derived from a genome-wide association study conducted in the UK Biobank population. The random effect inverse-variance weighted Mendelian randomization approach was used as the primary method and MR-Egger, weighted-median, and MR-PRESSO approaches were conducted as sensitivity analyses.

Results:

Genetically determined diverticular disease was associated with a higher risk of colorectal cancer (beta = 0.441, 95%CI: 0.081–0.801, P = 0.016) in the FinnGen population, but the association was not found in the UK Biobank (beta = 0.208, 95%CI: -0.291,0.532, P = 0.207). The positive association remained consistent direction in the three sensitivity analyses. In the stratified analysis in the FinnGen consortium, an association was found to exist between genetically predicted diverticular disease and colon cancer (beta = 0.489, 95%CI: 0.020–0.959, P = 0.041), rather than rectum cancer (beta = 0.328, 95%CI: -0.119-0.775, P = 0.151). Besides, we found a slight association between colorectal cancer and diverticular disease (beta = 0.007, 95%CI: 0.004–0.010, P < 0.001) when using colorectal cancer as exposome and diverticular disease as outcome. However, there is a large sample overlap in this step of analysis.

Conclusion:

This Mendelian randomization study suggests that diverticular disease may be a possible risk factor for colorectal cancer and colon cancer rather than rectum cancer in the FinnGen population.

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Title: Association between diverticular disease and colorectal cancer: a bidirectional mendelian randomization study
Authors: Yanxi Zhang
Han Zhang
Jinghan Zhu
Yazhou He
Peng Wang
Doudou Li
Xiaozhuan Liu
Wen Jin
Junxi Zhang
Chuan Xu
Zengli Yu
Xin Zhao
Lingling Cui
Publication date: 01-12-2023
Publisher: BioMed Central
Keywords: Colorectal Cancer
Colorectal Cancer
Colon Cancer
Colon Cancer
Published in: BMC Cancer / Issue 1/2023
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-023-10606-x

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Abstract

Background:

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