Dataset Information

Causal association between inflammatory bowel disease and 32 site-specific extracolonic cancers: a Mendelian randomization study.

ABSTRACT:

Background

The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers.

Methods

Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD patients, 5956 Crohn's disease (CD) patients, and 6968 ulcerative colitis (UC) patients. Three sources of cancer GWAS were selected as outcome data. Two-sample Mendelian randomization (MR) analysis was conducted to assess the causal effects of IBD on 32 extracolonic cancers. The meta-analysis was applied to assess the combined causal effect with multiple MR results.

Results

IBD, CD, and UC have potential causal associations with oral cavity cancer (IBD: OR = 1.180, 95% CI: 1.059 to 1.316, P = 0.003; CD: OR = 1.112, 95% CI: 1.008 to 1.227, P = 0.034; UC: OR = 1.158, 95% CI: 1.041 to 1.288, P = 0.007). Meta-analysis showed a significant positive causal relationship between IBD and breast cancer (OR = 1.059; 95% CI: 1.033 to 1.086; P < 0.0001) as well as a potential causal relationship between CD and breast cancer (OR = 1.029; 95% CI: 1.002 to 1.055; P = 0.032) based on combining multiple MR results.

Conclusions

This comprehensive MR analysis suggested that genetically predicted IBD, as well as its subtypes, may be a risk factor in the development of oral cavity and breast cancer.

SUBMITTER: Gao H

PROVIDER: S-EPMC10566178 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature

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Publications

Causal association between inflammatory bowel disease and 32 site-specific extracolonic cancers: a Mendelian randomization study.

Gao Hui H Zheng Shuhao S Yuan Xin X Xie Jiarong J Xu Lei L

BMC medicine 20231010 1

<h4>Background</h4>The risk of extracolonic cancer is increased in inflammatory bowel disease (IBD) patients, but it is not clear whether there is a causal relationship. We aimed to systematically estimate the causal relationship between IBD and extracolonic cancers.<h4>Methods</h4>Independent genetic variants strongly associated with IBD were extracted as instrumental variables from genome-wide association study (GWAS) conducted by the International IBD Genetics Consortium including 12,882 IBD ...[more]

PMID: 37817217

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Project description:Background and aimThe association between gallstones/cholecystectomy and cancer remains inconclusive in the current literature. This study aimed to explore the causal connections between gallstones/cholecystectomy and cancer risk by utilizing a bidirectional two-sample multivariable Mendelian randomization approach with Genome-Wide Association Studies data.MethodsUtilizing Genome-Wide Association Studies data from the UK Biobank and FinnGen, this research employed multivariable Mendelian randomization analyses to explore the impact of gallstones and cholecystectomy on the risk of 33 distinct cancer types. Instrumental variables for gallstones and cholecystectomy were carefully selected to ensure robust analyses, and sensitivity and heterogeneity tests were conducted to verify the findings' validity.ResultsMultivariable Mendelian randomization analysis, incorporating data from more than 450,000 individuals for gallstones and cholecystectomy, revealed nuanced associations with cancer risk. Cholecystectomy was associated with a significantly increased risk of nonmelanoma skin cancer (OR = 1.59, 95% CI: 1.21 to 2.10, P = 0.001), while gallstones were linked to a decreased risk of the same cancer type (OR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002). Interestingly, the analysis also suggested that cholecystectomy may lower the risk of small intestine tumors (OR = 0.18, 95% CI: 0.043 to 0.71, P = 0.015), with gallstones showing an inverse relationship, indicating an increased risk (OR = 6.41, 95% CI: 1.48 to 27.80, P = 0.013).ConclusionsThe multivariable Mendelian randomization analysis highlights the differential impact of gallstones and cholecystectomy on cancer risk, specifically for nonmelanoma skin cancer and small intestine tumors. These results underscore the importance of nuanced clinical management strategies and further research to understand the underlying mechanisms and potential clinical implications of gallstone disease and cholecystectomy on cancer risk.

Project description:IntroductionOver the past few years, multiple observational studies have speculated a potential association between inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn's disease (CD), and osteoporosis. However, no consensus has been reached regarding their interdependence and pathogenesis. Herein, we sought to further explore the causal associations between them.MethodsWe validated the association between IBD and reduced bone mineral density in humans based on genome-wide association studies (GWAS) data. To investigate the causal relationship between IBD and osteoporosis, we performed a two-sample Mendelian randomization study using training and validation sets. Genetic variation data for IBD, CD, UC, and osteoporosis were derived from published genome-wide association studies in individuals of European ancestry. After a series of robust quality control steps, we included eligible instrumental variables (SNPs) significantly associated with exposure (IBD/CD/UC). We adopted five algorithms, including MR Egger, Weighted median, Inverse variance weighted, Simple mode, and Weighted mode, to infer the causal association between IBD and osteoporosis. In addition, we evaluated the robustness of Mendelian randomization analysis by heterogeneity test, pleiotropy test, leave-one-out sensitivity test, and multivariate Mendelian randomization.ResultsGenetically predicted CD was positively associated with osteoporosis risk, with ORs of 1.060 (95% CIs 1.016, 1.106; p = 0.007) and 1.044 (95% CIs 1.002, 1.088; p = 0.039) for CD in the training and validation sets, respectively. However, Mendelian randomization analysis did not reveal a significant causal relationship between UC and osteoporosis (p > 0.05). Furthermore, we found that overall IBD was associated with osteoporosis prediction, with ORs of 1.050 (95% CIs 0.999, 1.103; p = 0.055) and 1.063 (95% CIs 1.019, 1.109; p = 0.005) in the training and validation sets, respectively.ConclusionWe demonstrated the causal association between CD and osteoporosis, complementing the framework for genetic variants that predispose to autoimmune disease.

Dataset Information

Causal association between inflammatory bowel disease and 32 site-specific extracolonic cancers: a Mendelian randomization study.

Background

Methods

Results

Conclusions

Publications

Causal association between inflammatory bowel disease and 32 site-specific extracolonic cancers: a Mendelian randomization study.

Similar Datasets

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