Dataset Information

Assessing the causality between thyroid and breast neoplasms: A bidirectional Mendelian randomization study.

ABSTRACT:

Aim

This study aimed to evaluate the association between thyroid neoplasms (TN) and the risk of developing breast neoplasms (BN) by assessing data on single nucleotide polymorphisms (SNPs) obtained from the Deutsches Krebsforschungszentrum (DKFZ) and Breast Cancer Association (BCAC).

Methods

Data on SNPs associated with TN and BN were obtained from DKFZ and BCAC, respectively. Secondary data analysis of all pooled data from genome-wide association studies (GWAS) was performed to identify the genetic loci closely associated with TN or BN as instrumental variables (IVs). To evaluate the causal relationship between TN and BN, a bidirectional Mendelian randomization (MR) analysis was performed using MR Egger regression, weighted median, inverse variance weighted (IVW) random effects model, simple mode, weighted mode, maximum likelihood, penalized weighted median, IVW radial, IVW fixed effects, and robust adjusted profile scores (RAPS) method.

Results

The MR in this study demonstrated a modest reverse causal relationship between TN and BN but a significant positive causal relationship between BN and TN.

Conclusions

The MR of this study provided genetic evidence suggesting an association between BN and TN; however, further research is warranted to explore the potential mechanism of interaction between these two malignancies. Moreover, general breast screening should be performed in individuals with TN, but TN screening should be reinforced in individuals with BN.

SUBMITTER: Li Z

PROVIDER: S-EPMC9760946 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Publications

Assessing the causality between thyroid and breast neoplasms: A bidirectional Mendelian randomization study.

Li Zhenqi Z Xia Lu L Li Xiangzhi X He Hongyang H

Frontiers in oncology 20221205

<h4>Aim</h4>This study aimed to evaluate the association between thyroid neoplasms (TN) and the risk of developing breast neoplasms (BN) by assessing data on single nucleotide polymorphisms (SNPs) obtained from the Deutsches Krebsforschungszentrum (DKFZ) and Breast Cancer Association (BCAC).<h4>Methods</h4>Data on SNPs associated with TN and BN were obtained from DKFZ and BCAC, respectively. Secondary data analysis of all pooled data from genome-wide association studies (GWAS) was performed to i ...[more]

PMID: 36544708

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Project description:Background and purpose Observational studies have shown that sarcopenia and diabetic nephropathy (DN), are closely related; however, the causal relationship is unclear. This study aims to address this issue using a bidirectional Mendelian randomization (MR) study. Methodology We data from genome-wide association studies including appendicular lean mass (n = 244,730), grip strength (right: n = 461,089, left: n = 461026), walking speed (n = 459,915), and DN (3283 cases and 181,704 controls) to conduct a bidirectional MR study. First, we conducted a Forward MR analysis to evaluate the causality of sarcopenia on the risk of DN from the genetic perspective with appendicular lean mass, grip strength, and walking speed as exposure and DN as the outcome. Then, DN as the exposure, we performed a Reverse MR analysis to determine whether DN impacted the appendicular lean mass, grip strength, and walking speed of the appendices. Finally, a series of sensitivity studies, such as heterogeneity tests, pleiotropy evaluations, and Leave-one-out analyses, were conducted to assess the MR analysis’s accuracy further. Results According to a forward MR analysis, a genetically predicted decrease in appendicular lean mass is associated with an increased risk of developing DN risk (inverse variance weighting[IVW]: odd ratio [OR] = 0.863, 95% confidence interval [CI] 0.767-0.971; P = 0.014). According to reverse MR results, grip strength decreased as DN progressed (IVW: right β = 0.003, 95% CI: - 0.021 to - 0.009, P = 5.116e-06; left β = 0.003, 95% CI: - 0.024 to - 0.012, P = 7.035e-09). However, the results of the other MR analyses were not statistically different. Conclusion Notably, our findings suggest that the causal relationship between sarcopenia and DN cannot be generalized. According to analysis of the individual characteristic factors of sarcopenia, reducing in appendicular lean mass increases the risk of developing DN and DN is linked to reduced grip strength. But overall, there is no causal relationship between sarcopenia and DN, because the diagnosis of sarcopenia cannot be determined by one of these factors alone.

Project description:BackgroundObservational studies and animal experiments had suggested a potential relationship between gut microbiota abundance and pathogenesis of endometriosis (EMs), but the relevance of this relationship remains to be clarified.MethodsWe perform a two-sample bidirectional Mendelian randomization (MR) analysis to explore whether there is a causal correlation between the abundance of the gut microbiota and EMs and the direction of causality. Genome-wide association study (GWAS) data ukb-d-N80, finn-b-N14-EM, and MiBinGen were selected. Inverse variance weighted (IVW), weighted median, and MR Egger are selected for causal inference. The Cochran Q test, Egger intercept test, and leave-one-out analysis are performed for sensitivity analyses.ResultsIn the primary outcome, we find that a higher abundance of class Negativicutes, genus Dialister, genus Enterorhabdus, genus Eubacterium xylanophilum group, genus Methanobrevibacter and order Selenomonadales predict a higher risk of EMs, and a higher abundance of genus Coprococcus and genus Senegalimassilia predict a lower risk of EMs. During verifiable outcomes, we find that a higher abundance of phylum Cyanobacteria, genus Ruminococcaceae UCG002, and genus Coprococcus 3 predict a higher risk of EMs, and a higher abundance of genus Flavonifracto, genus Bifidobacterium, and genus Rikenellaceae RC9 predict a lower risk of EMs. In primary reverse MR analysis, we find that EMs predict a lower abundance of the genus Eubacterium fissicatena group, genus Prevotella7, genus Butyricicoccus, family Lactobacillaceae, and a higher abundance of genus Ruminococcaceae UCG009. In verifiable reverse MR analysis, we find that EMs predict a lower abundance of the genus Ruminococcaceae UCG004 and a higher abundance of the genus Howardella.ConclusionOur study implies a mutual causality between gut microbiota abundance and the pathogenesis of EMs, which may provide a novel direction for EMs diagnosis, prevention, and treatment, may promote future functional or clinical analysis.

Dataset Information

Assessing the causality between thyroid and breast neoplasms: A bidirectional Mendelian randomization study.

Aim

Methods

Results

Conclusions

Publications

Assessing the causality between thyroid and breast neoplasms: A bidirectional Mendelian randomization study.

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