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

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

doi:10.1186/s12885-023-10606-x

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

BMC Cancer. 2023 Feb 10;23(1):137. doi: 10.1186/s12885-023-10606-x.

Authors

Yanxi Zhang^#^{1

2}, Han Zhang^#³, Jinghan Zhu^#⁴, Yazhou He⁵, Peng Wang^{3

6}, Doudou Li³, Xiaozhuan Liu², Wen Jin¹, Junxi Zhang⁷, Chuan Xu⁸, Zengli Yu^{3

7}, Xin Zhao⁹, Lingling Cui¹⁰

Affiliations

¹ The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China.
² Henan Provincial People's Hospital, Zhengzhou University, Zhengzhou, China.
³ College of Public Health, Zhengzhou University, 450001, Zhengzhou, Henan, China.
⁴ The Second School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China.
⁵ Department of oncology, West China School of Public Health and West China Fourth Hospital, Sichuan University, Chengdu, China.
⁶ Henan Key Laboratory of Tumor Epidemiology and State Key Laboratory of Esophageal Cancer Prevention & Treatment, Zhengzhou University, Zhengzhou, China.
⁷ NHC Key Laboratory of Birth Defects Prevention & Henan Key Laboratory of Population Defects Prevention, Zhengzhou, China.
⁸ Department of Oncology, Sichuan Provincial People's Hospital, Sichuan Academy of Medical Sciences, University of Electronic Science and Technology of China, Chengdu, China.
⁹ The Third Affiliated Hospital, Zhengzhou University, Zhengzhou, China.
¹⁰ College of Public Health, Zhengzhou University, 450001, Zhengzhou, Henan, China. cuilingling0613@163.com.

^# Contributed equally.

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.

Keywords: Colorectal cancer; Diverticular disease; Mendelian randomization.

MeSH terms

Colonic Neoplasms*
Diverticular Diseases*
Genome-Wide Association Study
Humans
Mendelian Randomization Analysis
Polymorphism, Single Nucleotide
Rectal Neoplasms*