Journal of Shanghai Jiao Tong University (Medical Science) >

2024 , Vol. 44 >Issue 6: 755 - 761

DOI: https://doi.org/10.3969/j.issn.1674-8115.2024.06.011

Evidence-based medicine

Analysis of impact of type 1 diabetes on colorectal cancer by using two-sample Mendelian randomization

  • Yang YU ,
  • Dan MENG ,
  • Yiwen QIU ,
  • Jian YUAN ,
  • Yingjie ZHU
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  • Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China
ZHU Yingjie, E-mail: lh2197@shutcm.edu.cn.

Received date: 2024-01-06

  Accepted date: 2024-02-28

  Online published: 2024-06-11

Supported by

Shanghai Municipal Key Clinical Specialty Construction Project(SHSLCZDZK03701)

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Abstract

Objective ·To investigate the potential causal relationship between type 1 diabetes and colorectal cancer by using Mendelian randomization (MR). Methods ·Two-sample bidirectional MR was used to investigate the causal relationship between type 1 diabetes and colorectal cancer. All research data were collected from the IEU Open GWAS Project database. The dataset of type 1 diabetes included 9 266 cases and 15 574 controls, with correlation analysis in 12 783 129 single nucleotide polymorphisms (SNPs); the dataset of colorectal cancer included 5 657 cases and 372 016 controls, with correlation analysis in 29 999 696 SNPs. The instrumental variables SNPs were screened. The results derived from the inverse-variance weighted (IVW) method were used as the main indicator of effect. The results derived from other four methods, namely MR-Egger regression, weighted median, simple mode, and weighted mode, were used as reference. Sensitivity was analyzed with the leave-one-out method. Heterogeneity was analyzed with Cochran's Q test by using both IVW and MR-Egger methods. Pleiotropy was analyzed with MR-pleiotropy function, and Steiger test was used for directional research. The colocation analysis was used to find out whether the causal relationship between type 1 diabetes and colorectal cancer was caused by the same SNP. The genetic correlation between 2 diseases was analyzed by using the linkage disequilibrium score regression (LDSC). All tests were analyzed by using R language software (version 4.3.1). Results ·After being screened, a total of 33 instrumental variables (SNPs) were used. The heterogeneity test results showed that there was heterogeneity among the SNPs (IVW and MR-Egger: P<0.05), so the effect evaluation was based on the results of the random effect model. MR analysis showed that type 1 diabetes had a significant causal effect on colorectal cancer (P<0.05) by using IVW, MR-Egger, weighted median and weighted mode. Sensitivity analysis showed that the results were stable. Pleiotropy was not detected in pleiotropy test (P>0.05). Steiger test showed that the effect of type 1 diabetes on colorectal cancer was not interfered with by the reverse effect. Reverse MR analysis showed no causal effect of colorectal cancer on type 1 diabetes (P>0.05). The results of colocalization analysis showed that the probability of H4 hypothesis was 45.7%, and the causal relationship between the 2 diseases was not caused by the same SNP in the gene sequences. LDSC analysis demonstrated that there was no genetic correlation between the two diseases. Conclusion ·Type 1 diabetes may promote colorectal cancer, but colorectal cancer has no effect on type 1 diabetes.

Key words： colorectal cancer; type 1 diabetes; Mendelian randomization

Cite this article

Yang YU , Dan MENG , Yiwen QIU , Jian YUAN , Yingjie ZHU . Analysis of impact of type 1 diabetes on colorectal cancer by using two-sample Mendelian randomization[J]. Journal of Shanghai Jiao Tong University (Medical Science), 2024 , 44(6) : 755 -761 . DOI: 10.3969/j.issn.1674-8115.2024.06.011

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