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Novel genetic association between obesity, colorectal cancer, and inflammatory bowel disease

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Abstract

Purpose

Obesity/overweight is an important risk factor for CRC and IBD. The aim of this study was to investigate the role of common genetic factors and haplotypes associated with obesity, CRC and IBD.

Methods

Significant GWAS variants associated with CRC, IBD or obesity were extracted from the GWAS catalog. The common variants between CRC-IBD, CRC-obesity or IBD-obesity were identified. Finally, the haplotypic structure between these diseases was identified, and SNP function analysis, gene-gene expression, protein-protein interactions, gene survival analysis and pathway analysis were performed with the results.

Results

While the results showed several common variants between CRC and IBD, IBD and obesity, and CRC and obesity identified in previous GWAS, rs3184504 was the only common variant for CRC-IBD-obesity (P ≤ 5E-8). The result also identified a haplotypic block AGCAGT (r2 ≥ 0.8 and D’≥0.08) associated with the common variants of CRC-IBD-obesity. These variants are located on the SH2B3 gene, whose expression level decreases in both colon and rectal cancers (P ≤ 1E-3) and which has protein-protein interaction with inflammation- and cancer-associated genes.

Conclusion

The rs3184504 variant and the novel haplotype AGCAGT co-occurred in CRC, IBD, obesity, and inflammation. This novel haplotype could potentially be used in genetic panels to identify CRC/IBD susceptibility in obese patients.

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Data availability

The data that support the findings of this study are available on request from the corresponding author.

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Authors and Affiliations

  1. North Research Center, Pasteur Institute of Iran, Amol, Iran

    Morteza Gholami

  2. Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Morteza Gholami

  3. Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran

    Morteza Gholami

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Correspondence to Morteza Gholami.

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Gholami, M. Novel genetic association between obesity, colorectal cancer, and inflammatory bowel disease. J Diabetes Metab Disord (2023). https://doi.org/10.1007/s40200-023-01343-w

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