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

Li, Zhenqi; Xia, Lu; Li, Xiangzhi; He, Hongyang

doi:10.3389/fonc.2022.973161

Cited by 6 publications

(7 citation statements)

References 33 publications

(35 reference statements)

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“…Genus Senegalimassilia were reported to be significantly associated with the production of enterolactone 37 . Meanwhile, Senegalimassilia might be a protective factor for hypertension as previous study reported 38 . However, Senegalimassilia was causally linked with ED in our study, which is inconsistent with the results of this study.…”

Section: Discussioncontrasting

confidence: 99%

“…37 Meanwhile, Senegalimassilia might be a protective factor for hypertension as previous study reported. 38 However, Senegalimassilia was causally linked with ED in our study, which is inconsistent with the results of this study. Due to little information of Senegalimassilia was disclosed, more evidence of causal association between Senegalimassilia and ED development is still needed.…”

Section: F I G U R Econtrasting

confidence: 99%

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Genetically proxied intestinal microbiota and risk of erectile dysfunction

Zhang,

Xiong,

Zhang

et al. 2023

Andrology

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BackgroundThe interaction between intestinal microbiota and erectile dysfunction (ED) is less investigated. This study was performed to explore the association between intestinal microbiota and ED.MethodsIn this two‐sample Mendelian randomization (MR) study, genetic variants of gut microbiota were obtained from MiBioGen consortium containing 18,340 individuals. Six methods including inverse variance weighting (IVW), MR‐Egger, weighted median, maximum likelihood, MR robust adjusted profile score, and MR pleiotropy residual sum and outlier were used to investigate the causal links between intestinal microbiota and ED. Furthermore, reverse MR analysis was performed to exclude the causal impact of ED on gut microbiota.ResultsAs revealed by the IVW estimator, the risks of ED were raised by genetically proxied Lachnospiraceae (OR: 1.27), Lachnospiraceae NC2004 group (OR: 1.17), Oscillibacter (OR: 1.20), Senegalimassilia (OR: 1.32) (All P < 0.05) and Tyzzerella‐3 (OR: 1.14, P < 0.05). It was observed that Ruminococcaceae UCG013 exerted protective effect against ED (OR: 0.77, P < 0.05). These results were consistent with other estimators in sensitivity analyses. In reverse MR analyses, genetic liability to ED did not alter the abundances of Lachnospiraceae, Lachnospiraceae NC2004 group, Oscillibacter, Senegalimassilia, Tyzzerella‐3, and Ruminococcaceae UCG013 (All P > 0.05). No heterogeneity and pleiotropy were detected by Cochran's Q‐test, MR‐Egger, and global test (All P > 0.05).ConclusionsThis study provided novel evidence that genetically proxied Lachnospiraceae, Lachnospiraceae NC2004 group, Oscillibacter, Senegalimassilia, Tyzzerella‐3, and Ruminococcaceae UCG013 had potentially causal effects on ED. Further studies are needed to clarify the biological mechanisms linking intestinal microbiota to ED.

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Section: Discussioncontrasting

confidence: 99%

Section: F I G U R Econtrasting

confidence: 99%

Genetically proxied intestinal microbiota and risk of erectile dysfunction

Zhang,

Xiong,

Zhang

et al. 2023

Andrology

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“…This latter study also detected a publication bias suggesting that more studies are required to conclude. A recent MR analysis [ 34 ] on the bidirectional association between these diseases suggests that breast cancer increases the risk of thyroid cancer while thyroid cancer slightly decreases the risk of breast cancer. However, this MR analysis was based on a small sample size GWAS for thyroid cancer (649 cases and 431 controls) and these results need to be confirmed.…”

Section: Discussionmentioning

confidence: 99%

Investigation of common genetic risk factors between thyroid traits and breast cancer

Lucotte,

Asgari,

Sugier

et al. 2023

Human Molecular Genetics

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Breast cancer (bc) risk is suspected to be linked to thyroid disorders, however observational studies exploring the association between bc and thyroid disorders gave conflicting results. We proposed an alternative approach by investigating the shared genetic risk factors between bc and several thyroid traits. We report a positive genetic correlation between bc and thyroxine (FT4) levels (corr = 0.13, p-value = 2.0x10−4) and a negative genetic correlation between bc and thyroid-stimulating hormone (TSH) levels (corr = −0.09, p-value = 0.03). These associations are more striking when restricting the analysis to estrogen receptor-positive bc. Moreover, the polygenic risk scores (PRS) for FT4 and hyperthyroidism are positively associated to bc risk (OR = 1.07, 95%CI: 1.00–1.13, p-value = 2.8x10−2 and OR = 1.04, 95%CI: 1.00–1.08, p-value = 3.8x10−2, respectively), while the PRS for TSH is inversely associated to bc risk (OR = 0.93, 95%CI: 0.89–0.97, p-value = 2.0x10−3). Using the PLACO method, we detected 49 loci associated to both bc and thyroid traits (p-value<5x10−8), in the vicinity of 130 genes. An additional colocalization and gene-set enrichment analyses showed a convincing causal role for a known pleiotropic locus at 2q35 and revealed an additional one at 8q22.1 associated to both bc and thyroid cancer. We also found two new pleiotropic loci at 14q32.33 and 17q21.31 that were associated to both TSH levels and bc risk. Enrichment analyses and evidence of regulatory signals also highlighted brain tissues and immune system as candidates for obtaining associations between bc and TSH levels. Overall, our study sheds light on the complex interplay between bc and thyroid traits and provides evidence of shared genetic risk between those conditions.

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“…21 Thus, MR can examine the causality between exposures and outcomes and it has been widely used in the field of cardiovascular diseases and oncology. [22][23][24][25][26] In the present study, we conducted bidirectional MR analyses to explore a potential causality relationship between AF and breast cancer, which may provide some novel insights and evidence in this field of research.…”

Section: Introductionmentioning

confidence: 99%

“…Mendelian randomization (MR) is a method utilizing genetic variants (randomly allocated from parents to offspring) as proxies for the exposure of interest to give insights for causal relationships, preventing bias from confounding factors and reverse causation 21 . Thus, MR can examine the causality between exposures and outcomes and it has been widely used in the field of cardiovascular diseases and oncology 22–26 . In the present study, we conducted bidirectional MR analyses to explore a potential causality relationship between AF and breast cancer, which may provide some novel insights and evidence in this field of research.…”

Section: Introductionmentioning

confidence: 99%

Causal associations between atrial fibrillation and breast cancer: A bidirectional Mendelian randomization analysis

Gong,

Hu,

Yang

et al. 2024

Cancer Medicine

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BackgroundPrevious observational studies indicated that atrial fibrillation may increase the risk of breast cancer. Following a breast cancer diagnosis, the chance of developing atrial fibrillation may increase as well. However, it is uncertain whether the link is causal or just due to confounding factors.ObjectiveUsing bidirectional Mendelian randomization (MR) analysis, we sought to assess the bidirectional causal relationship between atrial fibrillation and breast cancer from a genetic level.MethodsLarge genome‐wide association studies yielded summary‐level data for atrial fibrillation and breast cancer. The preliminary estimate was inverse variance weighted (IVW) under a random model. MR–Egger, weighted median, simple mode, weighted mode, and multivariable MR (adjusting body mass index, smoking, and alcohol drinking) were performed as sensitivity analyses.ResultsGenetically predicted atrial fibrillation presented no statistically significant association with overall breast cancer (odds ratio [OR] = 1.00; 95% confidence interval [CI]: 0.97–1.04; p = 0.79), estrogen receptor (ER) + (OR = 1.00; 95% CI: 0.96–1.03; p = 0.89) or ER− subtypes (OR = 1.00; 95% CI: 0.97–1.04; p = 0.89). Similarly, genetically predicted overall breast cancer (OR = 1.01; 95% CI: 0.98–1.04; p = 0.37), ER+ (OR = 1.02; 95% CI: 0.99–1.05; p = 0.16) or ER− (OR = 0.98; 95% CI: 0.93–1.02; p = 0.32) subtypes had no causal effect on atrial fibrillation. Sensitivity analyses yielded similar results. Individual single nucleotide polymorphism had little effect on the total estimate. We did not observe any evidence of horizontal pleiotropy.ConclusionsOur bidirectional MR studies revealed that there may be no causal links between atrial fibrillation and breast cancer.

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

Cited by 6 publications

References 33 publications

Genetically proxied intestinal microbiota and risk of erectile dysfunction

Genetically proxied intestinal microbiota and risk of erectile dysfunction

Investigation of common genetic risk factors between thyroid traits and breast cancer

Causal associations between atrial fibrillation and breast cancer: A bidirectional Mendelian randomization analysis

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