Abstract
OBJECTIVE: Observational studies have suggested a potential association between constipation and several cancers. However, the causal relationship between constipation and cancer remains unclear. The purpose of this study is to explore the potential causal relationship between constipation and pan-cancer using Mendelian Randomization (MR) methods. METHODS: We performed a bidirectional MR analysis using publicly available summary data from Genome-Wide Association Studies (GWAS) statistics. The Inverse Variance Weighted (IVW) method was used as the main analysis method. We also used four MR methods: MR-Egger, Weighted Median, MR-PRESSO and MR.RAPS. Simultaneously, MR-Egger regression, Cochran's Q test and MR-PRESSO Global test were used to estimate the pleiotropy and heterogeneity of SNPs. In addition, we performed "leave-one-out" analyses" to avoid bias caused by horizontal pleiotropy of individual SNPs. RESULTS: MR analysis revealed a potential causal association between constipation and the risk of colorectal cancer (CRC) [IVW (OR= 1.0021 (1.0003, 1.0039), P= 0.0234)], lung cancer (LC) [IVW (OR=1.0955 (1.0134, 1.1843), P=0.0218)], Oral cavity and pharyngeal cancer (OPC) [IVW (OR=1.4068 (1.0070, 1.9652), P=0.0454)], and Pancreatic cancer (PC) [IVW (OR=1.5580 (1.0659, 2.2773), P=0.0221)]. In addition, we explored causal relationships between constipation and 12 other types of cancers, including gastric cancer, esophageal cancer, skin melanoma and so on. All five methods yielded no evidence of a causal association between constipation and the risk of these cancer types. In the reverse MR analysis, there was no evidence of a causal association between cancer and the risk of constipation for all five methods. CONCLUSION: Our bidirectional MR study suggests a potential relationship between constipation and an increased risk of CRC, LC OPC and PC. The underlying mechanisms behind these associations will need to be explored in future experimental studies.