Evidence map›Paper›PMID 42068645›Full record

ArticleClinics (Sao Paulo, Brazil)2026

Genetically predicted TTK inhibition and its association with reduced breast cancer risk: a two-step Mendelian randomization study of potential gut microbiome mediation.

Jia Liu, Mohan Liu, Ying Xu, Zihao Wang, Xingtong Zhou, Qiang Sun

Abstract read
In one paragraph

Article in Clinics (Sao Paulo, Brazil), 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Jia LiuDepartment of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Mohan LiuDepartment of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Ying XuDepartment of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Zihao WangDepartment of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.
Xingtong ZhouDepartment of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China. Electronic address: zhouxingtong@pumch.cn.
Qiang SunDepartment of Breast Surgery, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundBOS172722, a selective TTK inhibitor, shows promise for Breast Cancer (BC) treatment. The role of gut microbiota as a potential mediator in this process has not been established. This Mendelian Randomization (MR) study investigated the causal effect of TTK inhibition on BC and conducted an exploratory analysis of potential mediation by gut microbiota.

methodsA two-step, two-sample drug target MR analysis used IEU Open GWAS project datasets. The inverse-variance-weighted method estimated causal effects, with sensitivity tests confirming robustness. False Discovery Rate (FDR) correction was applied to analyses for all microbial taxa.

resultsGenetically predicted TTK inhibition significantly reduced BC risk (OR = 0.667, 95 % CI 0.543-0.819; FDR-adjusted p < 0.001). In secondary analyses, initial uncorrected results indicated nominal associations between TTK inhibition and 20 gut microbial taxa, and between 6 taxa and BC risk. However, none of these microbiota-related associations remained statistically significant after FDR correction (all q-values >0.1). An exploratory mediation analysis on Genus Anaerostipes id.1991, which showed the strongest nominal signals (TTK inhibition on Anaerostipes: uncorrected p = 0.003; Anaerostipes on BC: uncorrected p = 0.025), was performed for hypothesis generation only; no statistically significant mediation was observed.

conclusionThis study provides robust genetic evidence that TTK inhibition is causally associated with a decreased risk of breast cancer. The exploratory analysis of gut microbiota as a mediator did not yield statistically significant results after correction for multiple testing. The potential role of specific microbes, such as Genus Anaerostipes, remains inconclusive and requires further dedicated investigation.

Indexed as

Breast cancerCausalityDrug target MRGut microbiotaMediation analysisMendelian randomizationTTK inhibition

Identifiers

PMID42068645
PMCPMC13147426

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.