Causal Relationship Between Gut Microbiota and Gynecological Cancer:A
Two-Sample Mendelian Randomization Study
Abstract
Background: Previous research has demonstrated a correlation between changes in
the composition of the gut microbiota and multiple gynecological tumors.However,
the causal relationship between the gut microbiota and gynecological tumors remains
unclear.Therefore, this study employs a two-sample Mendelian randomization (MR)
analysis to investigate the causal association between the gut microbial community
and common gynecological tumors. The aim is to identify specific pathogenic
bacterial communities that may be associated with the occurrence of gynecological
tumors.
Materials and Methods: We utilized data from the MiBioGen consortium’s
Genome-Wide Association Study (GWAS) on gut microbiota as the exposure variable.
Four common gynecological tumors, including uterine fibroids, endometrial cancer,
ovarian cancer, and cervical cancer, were selected as outcome variables. Single
nucleotide polymorphisms (SNPs) significantly associated with the exposure were
chosen as instrumental variables (IVs). The inverse variance-weighted(IVW) method
was used as the primary MR analysis to evaluate the causal relationship between gut
microbiota and these tumors, aiming to identify microbial communities associated
with the development of gynecological tumors. Further validation was conducted in a
independent validation cohort. Sensitivity analyses were performed to ensure the
robustness of the results. Finally, reverse MR analysis was conducted to assess the
potential for reverse causality.
Results: Combining the results from the discovery and validation cohorts, we found
that a higher relative abundance of Lachnospiraceae was associated with a lower risk
of uterine fibroids (OR: 0.882, 95% CI: 0.793-0.999, P = 0.982). Conversely, a higher
risk of ovarian cancer was associated with a higher relative abundance of
Lachnospiraceae (OR: 1.329, 95% CI: 1.019-1.732, P= 0.036). Sensitivity analyses
confirmed the robustness of these findings. Furthermore, the results of the reverse MR
analysis showed no evidence of a reverse causal relationship between uterine fibroids,
ovarian cancer, and Lachnospiraceae.
Conclusion: This study indicate a causal association between Lachnospiraceae and
uterine fibroids and ovarian cancer.This provides new insights into the role of gut
microbiota in the mechanism of gynecological tumor development.
Introduction
In recent years, cancer has become the leading cause of death among urban
residents and the second leading cause among rural residents. The incidence and
mortality rates of gynecological tumors continue to rise, posing a significant threat to
women's health. Among these tumors, uterine fibroids are the most common. Cervical
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