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ORIGINAL RESEARCH article

Front. Oncol.
Sec. Cancer Epidemiology and Prevention
Volume 14 - 2024 | doi: 10.3389/fonc.2024.1428003
This article is part of the Research Topic Application of Novel Genetic and Statistical Approaches in the Era of Personalized Medicine: Individual Cancer Risk Estimation and Patients' Therapeutic Strategy Decision View all articles

Causal associations between constipation and pan-cancer: a bidirectional Mendelian randomization study

Provisionally accepted
Yongze Dang Yongze Dang 1Xinyu He Xinyu He 1Xiaoxiao Liu Xiaoxiao Liu 1Yuchen Wang Yuchen Wang 1*Shangyi Geng Shangyi Geng 1*Yutong Cheng Yutong Cheng 2*Hongbing Ma Hongbing Ma 1*Xixi Zhao Xixi Zhao 1*
  • 1 Department of Radiation Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
  • 2 Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, Shaanxi Province, China

The final, formatted version of the article will be published soon.

    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.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.Conclusions：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. 删除了: Simple Mode and Weighted Mode 62 删除了: MR-Egger regression and Cochran's Q test were 63 used to estimate the pleiotropy and heterogeneity of SNPs.

    Keywords: consitipation, pan cancer, Mendelian Randomization, GWAS, causality

    Received: 05 May 2024; Accepted: 26 Aug 2024.

    Copyright: © 2024 Dang, He, Liu, Wang, Geng, Cheng, Ma and Zhao. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence:
    Yuchen Wang, Department of Radiation Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
    Shangyi Geng, Department of Radiation Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
    Yutong Cheng, Department of Gastroenterology, Second Affiliated Hospital of Xi'an Jiaotong University, Xi’an, 710004, Shaanxi Province, China
    Hongbing Ma, Department of Radiation Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China
    Xixi Zhao, Department of Radiation Oncology, Second Affiliated Hospital of Xi’an Jiaotong University, Xi'an, China

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