Title:Causal Relationships of Chronic Constipation and Irritable Bowel Syndrome with Digestive Tract Cancers: A Mendelian Randomization Study
Volume: 19
Author(s): Rencai Fan*, Jiaqi Zhang, Jiaofeng Shen, Chenkai Mao, Shicheng Li and Zhixiang Zhuang
Affiliation:
- Department of Oncology, The Second Affiliated Hospital of Soochow University, No.1055, Sanxiang Road, Gusu District,
Soochow 215004, Jiangsu Province, P.R. China
Keywords:
Constipation, irritable bowel syndrome, digestive tract cancers, mendelian randomization, European cohorts, esophageal malignancy (ESCA).
Abstract: Background: Chronic constipation and irritable bowel syndrome (IBS) manifest as
prevalent gastrointestinal disorders, while digestive tract cancers (DTCs) present formidable
challenges to global well-being. However, extant observational studies proffer uncertain insights
into potential causal relationships of constipation and IBS with susceptibility to DTCs.
Methods: We executed Mendelian randomization (MR) analysis to establish causal connections
between these conditions and seven distinct categories of DTCs, including colorectal carcinoma
(CRC), hepatocellular cancer (HCC), esophageal malignancy (ESCA), pancreatic adenocarcinoma
(PAAD), biliary tract carcinoma (BTCs), gastric carcinoma (GC), and small intestine neoplasm
(SIC). Leveraging instrumental variables (IVs) obtained from GWAS data of the FinnGen
database, we employed a range of analytical methodologies, including inverse-variance
weighting multiplicative random effects (IVW_MRE), inverse-variance weighting fixed effects
(IVW_FE), maximum likelihood (ML), weighted median (WM), MR‒Egger regression, and the
MR-PRESSO test.
Results: We observed a substantial linkage between genetically predicted constipation and increased
vulnerability to PAAD (OR = 2.29, 95% CI: 1.422-3.69, P = 0.001) via the IVW method.
Following the removal of outlier SNPs through MR-PRESSO, genetically predicted IBS
was affiliated with an increased risk of CRC (OR = 1.17, 95% CI: 1-1.37, P = 0.05). Nonetheless,
decisive causal correlations of constipation or IBS with other DTCs remain elusive.
Conclusion: In summary, genetically predicted constipation was associated with an augmented
PAAD risk, and IBS was associated with an increased CRC susceptibility within European cohorts,
in agreement with some observational studies. Nevertheless, the causal associations of
constipation and IBS with other DTCs remain inconclusive.
