Casual effects of type 1 diabetes mellitus on site-specific digestive cancers - a Mendelian randomisation analysis

Q: What is the main objective of the study?

To determine whether type 1 diabetes mellitus (T1DM) has a causal relationship with the risk of digestive cancers.

Q: Which digestive cancer types were assessed in the Mendelian randomisation analysis?

Six types were analyzed: oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, pancreatic cancer, and colorectal cancer.

Q: Did the study find causal effects of T1DM on all digestive cancers?

No. No significant causal effects were observed for oesophageal, stomach, hepatocellular, biliary tract, or pancreatic cancers, but a causal positive association between T1DM and colorectal cancer was identified.

Sep 21, 2026

Uploaded by Levi

Despite conflicting results from observational research, the causal link between type 1 diabetes mellitus (T1DM) and digestive cancer risk remains uncertain. This Mendelian randomisation study evaluates whether T1DM causally affects six major digestive cancers using genome-wide association study summary data from 1,588,872 participants. Instrumental variables comprised 35 T1DM-associated single nucleotide polymorphisms. No significant causal effects were found for oesophageal, stomach, hepatocellular, biliary tract, or pancreatic cancers, whereas a positive causal association with colorectal cancer was identified, with sensitivity analyses showing no heterogeneity or horizontal pleiotropy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages10

Reading Time25 min

AccessFree to download

Objective

Methods

Study design and data

Sensitivity analyses

Results

Conclusions

TYPE Original Research PUBLISHED 05 September 2024 DOI 10.3389/fendo.2024.1407329 OPEN ACCESS EDITED BY Thiago Quinaglia A. C. Silva, Massachusetts General Hospital, United States REVIEWED BY Joaquim Barreto, State University of Campinas, Brazil Fengyun Wu, Characteristic Medical Center of Chinese People’s Armed Police Force, China Han Yang, Hospital of Chengdu University of Traditional Chinese Medicine, China Xiang Xiao, Hospital of Chengdu University of Traditional Chinese Medicine, China, in collaboration with reviewer HY *CORRESPONDENCE Weiming Deng [dengweim@mail2.sysu.edu.cn](dengweim@mail2.sysu.edu.cn) †These authors have contributed equally to this work RECEIVED 26 March 2024 ACCEPTED 17 July 2024 PUBLISHED 05 September 2024 CITATION Zhao J, Li W, Chen L, Li M and Deng W (2024) Casual effects of type 1 diabetes mellitus on site-speciﬁc digestive cancers: a Mendelian randomisation analysis. Front. Endocrinol. 15:1407329 . doi: 10.3389/fendo.2024.1407329 COPYRIGHT © 2024 Zhao, Li, Chen, Li and Deng. 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) and the copyright owner(s) 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. Casual effects of type 1 diabetes mellitus on site-speciﬁc digestive cancers: a Mendelian randomisation analysis Jinli Zhao 1†, Wenjin Li 2†, Libo Chen 3, Mingyong Li 3 and Weiming Deng 3* 1 Department of Emergency Medicine, The First Afﬁliated Hospital, Hengyang Medical School, University of South China, Hengyang, China, 2 Department of Nutrition, The Second Afﬁliated Hospital, Hengyang Medical School, University of South China, Hengyang, China, 3 Department of Urology, The First Afﬁliated Hospital, Hengyang Medical School, University of South China, Hengyang, China Objective: Despite several observational studies attempting to investigate the potential association between type 1 diabetes mellitus (T1DM) and the risk of digestive cancers, the results remain controversial. The purpose of this study is to examine whether there is a causal relationship between T1DM and the risk of digestive cancers. Methods: We conducted a Mendelian randomisation (MR) study to systematically investigate the effect of T1DM on six most prevalent types of digestive cancers (oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, pancreatic cancer, and colorectal cancer) . A total of 1,588,872 individuals were enrolled in this analysis, with 372,756 being the highest number for oesophageal cancer and 3,835 being the lowest for pancreatic cancer. Multiple MR methods were performed to evaluate the causal association ofT1DM with the risk of six site-speciﬁc cancers using genome-wide association study summary data. Sensitivity analyses were also conducted to assess the robustness of the observed associations. Results: We selected 35 single nucleotide polymorphisms associated with T1DM as instrumental variables. Our ﬁndings indicate no signiﬁcant effect of T1DM on the overall risk of oesophageal cancer (OR= 0.99992, 95% CI: 0.99979-1.00006, P= 0.2866), stomach cancer (OR=0.9298,95% CI: 0.92065-1.09466, P= 0.9298), hepatocellular carcinoma (OR= 0.99994,95% CI: 0.99987-1.00001, P= 0.1125), biliary tract cancer (OR=0.97348,95% CI: 0.8079-1.1729, P= 0.7775)), or pancreatic cancer (OR =1 . 01258, 95% CI: 0 .96243-1. 06533, P= 0 . 6294) . However, we observed a causal association between T1DM and colorectal cancer (OR=1.000, 95% CI: 1.00045-1.0012, P<0.001), indicating that T1DM increases the risk of colorectal cancer. We also performed sensitivity analyses, which showed no heterogeneity or horizontal pleiotropy. For the reverse MR

FAQs

What is the main objective of the study?

To determine whether type 1 diabetes mellitus (T1DM) has a causal relationship with the risk of digestive cancers.

Which digestive cancer types were assessed in the Mendelian randomisation analysis?

Six types were analyzed: oesophageal cancer, stomach cancer, hepatocellular carcinoma, biliary tract cancer, pancreatic cancer, and colorectal cancer.

Did the study find causal effects of T1DM on all digestive cancers?

No. No significant causal effects were observed for oesophageal, stomach, hepatocellular, biliary tract, or pancreatic cancers, but a causal positive association between T1DM and colorectal cancer was identified.

Sep 21, 2026

Uploaded by Levi