World Journal of Oncology, ISSN 1920-4531 print, 1920-454X online, Open Access
Article copyright, the authors; Journal compilation copyright, World J Oncol and Elmer Press Inc
Journal website https://www.wjon.org

Original Article

Volume 14, Number 6, December 2023, pages 558-569

Genetically Predicted Causal Effects of Gut Microbiota and Gut Metabolites on Digestive Tract Cancer: A Two-Sample Mendelian Randomization Analysis

Figures

Figure 1.
Figure 1. Study design of the two-sample MR for the effect of the genetically predicted gut microbiome and gut metabolites on digestive tract cancer. MiBioGen: international consortium MiBioGen; TwinsUK Registry: the UK adult twin registry; FHS: Framingham Heart Study; LD: linkage disequilibrium; SNP: single-nucleotide polymorphism; MR: Mendelian randomization; IVs: instrumental variables; IVW: inverse-variance weighted.
Figure 2.
Figure 2. Causal effects of gut microbiome and digestive tract cancer based on the IVW method (SNPs with P < 5 × 10-8). (a) Heatmap of the P-value. Red color in the heatmap indicates a positive correlation between gut microbiome and digestive tract cancer and blue color indicates a negative correlation. The color depth represents the size of the P-value, with darker colors indicating more significant P-values. (b) Network interactions based on statistically significant ORs. Color and line thickness in the network diagram indicate the OR of gut microbiota and digestive tract cancer. Darker red color and thicker lines indicate higher OR values. (c) Forest plot with statistically significant ORs. OR > 1 indicates the positive correlation between a particular gut microbiota and a particular digestive tract cancer. OR < 1 indicates the negative correlation between the two. IVW: inverse-variance weighted; GM: gut microbiome; SNP: single-nucleotide polymorphism; OR: odds ratio; 95% CI: 95% confidence interval; NSNP: number of SNP.
Figure 3.
Figure 3. Causal effects of gut metabolite and digestive tract cancer based on the IVW method (SNPs with P < 1 × 10-5). (a) Heatmap of the ORs. Color in the heatmap indicates the OR of gut metabolite and digestive tract cancer. Darker red color indicates higher OR values. The asterisk indicates statistically significant OR. (b) Correlation between GABA and colorectal cancer. IVW: inverse-variance weighted; SNP: single-nucleotide polymorphism; OR: odds ratio; MR: Mendelian randomization.

Table

Table 1. Description of Gut Microbiota, Metabolites, and Digestive Tract Cancer
 
TraitsConsortiumSample sizePopulationsYearJournal
Gut
  Gut microbiotaMiBioGen18,340 individualsEuropean2021Nature Genetics
TwinsUK Registry1,126 individualsEuropean2016Cell Host & Microbe
  Gut metabolitesFHS2,076 individualsEuropean2013Cell Metabolism
Cancer
  Digestive tract cancerFinnGen (R8)9,822 casesEuropean2022Nature
  Esophagus cancerFinnGen (R8)503 casesEuropean2022Nature
  Stomach cancerFinnGen (R8)1,227 casesEuropean2022Nature
  Bile duct cancerFinnGen (R8)227 casesEuropean2022Nature
  Liver cancerFinnGen (R8)648 casesEuropean2022Nature
  Pancreatic cancerFinnGen (R8)1,249 casesEuropean2022Nature
  Colorectal cancerFinnGen (R8)5,458 casesEuropean2022Nature