A two-step, two-sample Mendelian randomization analysis investigating the interplay between gut microbiota, immune cells, and melanoma skin cancer

Medicine (Baltimore). 2024 Nov 8;103(45):e40432. doi: 10.1097/MD.0000000000040432.

Abstract

This study aims to rigorously explore the potential causal relationships among gut microbiota (GM), immune cells, and melanoma skin cancer among participants from Europe, where this disease exhibits significant prevalence and profound societal impact. Using the genome-wide association analysis database, a double-sample Mendelian randomization (MR) analysis was drawn upon to investigate GM, immune cells, and melanoma skin cancer. The inverse variance weighted approach was applied to estimate the causal connections among these variables. A two-step MR analysis was employed to quantitatively gauge the impact of immune cells mediated GM on melanoma skin cancer. To address potential sources of bias, such as pleiotropy and heterogeneity, multiple analytical techniques were integrated. The MR analysis pinpointed 6 GM taxa related to either an augmented or declined risk of late-stage melanoma skin cancer. In the same vein, 32 immune cell phenotypes were noticed as correlates with modified risk of melanoma skin cancer. Our study also implies that the probable association between GM and melanoma could be facilitated by 5 immune cell phenotypes. The findings of our study underline certain GM taxa and immune cells as potential influencers on the onset and development of melanoma skin cancer. Importantly, our results spotlight 5 immune cell phenotypes as potential agents mediating this association.

MeSH terms

  • Europe / epidemiology
  • Gastrointestinal Microbiome*
  • Genome-Wide Association Study*
  • Humans
  • Melanoma* / genetics
  • Melanoma* / immunology
  • Melanoma, Cutaneous Malignant
  • Mendelian Randomization Analysis*
  • Skin Neoplasms* / genetics
  • Skin Neoplasms* / immunology
  • Skin Neoplasms* / microbiology