Dataset Information

The causal effect of atopic dermatitis on lung cancer: A Mendelian randomization study.

ABSTRACT:

Background

Growing evidence has shown that atopic dermatitis (AD) may decrease lung cancer (LC) risk. However, the causality between the two diseases is inconsistent and controversial. Therefore, we explored the causal relationship between AD and different histological subtypes of LC by using the Mendelian randomization (MR) method.

Materials and methods

We conducted the MR study based on summary statistics from the genome-wide association studies (GWAS) of AD (10,788 cases and 30,047 controls) and LC (29,266 cases and 56,450 controls). Instrumental variables (IVs) were obtained after removing SNPs associated with potential confounders. We employed inverse-variance weighted (IVW), MR-Egger, and weighted median methods to pool estimates, and performed a comprehensive sensitivity analysis.

Results

The results of the IVW method suggested that AD may decrease the risk of developing lung adenocarcinoma (LUAD) (OR = 0.91, 95% CI: 0.85-0.97, P = 0.007). Moreover, no causality was identified between AD and overall LC (OR = 0.96, 95% CI: 0.91-1.01, P = 0.101), lung squamous cell carcinoma (LUSC) (OR = 1.04, 95% CI: 0.96-1.036, P = 0.324), and small cell lung carcinoma (SCLC) (OR = 0.95, 95% CI: 0.82-1.10, P = 0.512). A comprehensive sensitivity test showed the robustness of our results.

Conclusion

The present study indicates that AD may decrease the risk of LUAD in the European population, which needs additional investigations to identify the potential molecular mechanisms.

SUBMITTER: Huang P

PROVIDER: S-EPMC11224128 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Publications

The causal effect of atopic dermatitis on lung cancer: A Mendelian randomization study.

Huang Peng P Wen Feng F Wu QiuJi Q Zhang PengFei P Li Qiu Q

Skin research and technology : official journal of International Society for Bioengineering and the Skin (ISBS) [and] International Society for Digital Imaging of Skin (ISDIS) [and] International Society for Skin Imaging (ISSI) 20240701 7

<h4>Background</h4>Growing evidence has shown that atopic dermatitis (AD) may decrease lung cancer (LC) risk. However, the causality between the two diseases is inconsistent and controversial. Therefore, we explored the causal relationship between AD and different histological subtypes of LC by using the Mendelian randomization (MR) method.<h4>Materials and methods</h4>We conducted the MR study based on summary statistics from the genome-wide association studies (GWAS) of AD (10,788 cases and 30 ...[more]

PMID: 38965791

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Project description:BackgroundSome evidence suggests abnormalities in fatty acids in patients with atopic dermatitis (AD), and benefits of supplementation with these fatty acids have been reported. However, there is still substantial controversy on the correlation between fatty acids and AD. Therefore, the aim of this study was to determine whether fatty acid levels are causally related to AD using a Mendelian randomization approach.MethodsWe evaluated the data about the fatty acids levels and AD with various methods from Genome-Wide Association Study (GWAS). GWAS results were available both from European ancestry. Mendelian randomization methods were used to analysis the casual inference of fatty acids on AD. MR Egger and MR-PRESSO were used to determine pleiotropy and heterogeneity. Further analysis was conducted using instruments associated with the FADS genes to address mechanisms involved. We also used Multivariate MR (MVMR) to show the independent casual inference of omega-3 (n-3) fatty acids on AD.ResultsMendelian randomization (MR) analysis suggests that n-3 fatty acid levels are associated with a lower risk of AD (n-3 ORIVW: 0.92, 95% confidence interval [CI]: 0.87-0.98; p = 0.01). Moreover, docosahexaenoic acids (DHA) levels, which is a kind of long-chain, highly unsaturated omega-3 (n-3) fatty acid, and its higher level was associated with a lower risk of AD (DHA ORIVW: 0.91, 95% CI: 0.84-0.98; p = 0.02). We ran multivariable MR analysis while controlling for variables within the other types of fatty acids. The effect estimates agreed with the preliminary MR analysis indicating the effect of n-3 fatty acids levels on AD was robust. MR-egger suggest no significant pleiotropy and heterogeneity on genetic instrumental variants. Outliers-corrected MR analyses after controlling horizontal pleiotropy were still robust. The single-SNP analyses revealed that n-3 fatty acids are likely linked to a decreased risk of AD through FADS cluster, highlighting the significance of the FADS gene in the fatty acids synthesis pathway in the development of AD.ConclusionOur studies suggest that n-3 fatty acids may reduce the risk of AD. Risk prediction tools based on n-3 fatty acid levels may be valuable methods for improving AD screening and primary prevention. To reduce the risk of AD, individuals could enhance n-3 fatty acids intake through supplement or diet.

Project description:Accumulating evidence indicates a correlation between gut microbiota (GM) and atopic dermatitis (AD). Nevertheless, the causal relationship between specific pathogenic bacterial taxa and AD remains uncertain. This investigation utilized a two-sample Mendelian randomization (MR) analysis to assess the causal association between GM and AD, identifying the most influential GM taxa. An MR study was conducted utilizing summary statistics derived from genome-wide association studies encompassing 207 GM taxa and their association with AD risk. The genome-wide association studies summary statistics for 207 GM taxa (from phylum to species level) were generated by the Dutch Microbiome Project. The genetic variants (P < 1 × 10-5) correlated with GM (n = 7738) were identified from this investigation. Additionally, 4 supplementary MR approaches, simple mode, MR-Egger, weighted mode, and weighted median, supported the inverse-variance weighted approach. Furthermore, sensitivity analyses were executed using leave-one-out analysis, Cochran Q test, MR-Egger intercept test, MR pleiotropy residual sum and outlier global test, and MR Steiger test. The MR analysis identified 17 distinct bacterial taxa involving 2 orders, 4 families, 5 genera, and 6 species. The inverse-variance weighted method demonstrated that 6 bacterial taxa were positively associated with AD. These taxa included the order Pasteurellales, family Burkholderiales noname, family Pasteurellaceae, genus Burkholderiales noname, species Burkholderiales bacterium_1_1_47, and species Desulfovibrio piger. Eleven bacterial taxa were negatively associated with AD, comprising the order Actinomycetales, family Micrococcaceae, family Oscillospiraceae, genus Rothia, genus Collinsella, genus Oscillibacter, genus Pseudoflavonifractor, species Oscillibacter_unclassified, species Roseburia hominis, species R mucilaginosa, and species Parabacteroides merdae. Moreover, the MR-Egger intercept test and MR pleiotropy residual sum and outlier global test validated that the MR analysis remained unaffected by horizontal pleiotropy (P > .05). Furthermore, the leave-one-out analysis contributed to validating the robustness of the outcomes. Finally, an MR Steiger directionality test confirmed the assessment of potential causal direction (P < .001). This investigation identified specific intestinal flora causally associated with AD risk, offering novel insights for future investigations and innovative avenues for AD diagnosis, therapeutic intervention, and prognostic assessment.

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Project description:ObjectivesNumerous observational studies have reported associations between circulating cytokines and atopic dermatitis (AD); however, the causal relationships between them remain unclear. To explore the causal correlations and direction of causal effects between AD and levels of 91 circulating cytokines.MethodsTwo-sample Mendelian randomization (MR) analyses were conducted to examine the causal relationships between 91 circulating cytokines and AD using summary statistics from genome-wide association studies (GWAS). Reverse MR analyses were performed to investigate reverse causation. Pleiotropy and heterogeneity tests were conducted to assess the robustness of the findings. Additional transcriptome database and clinical peripheral blood mononuclear cells (PBMCs) samples were utilized to validate the results of MR analyses.ResultsLevels of interleukin (IL)-13, IL-18 Receptor 1, Tumor necrosis factor ligand superfamily member 14 (TNFSF14), TNF-related activation-induced cytokine (TRANCE), C-X-C motif chemokine (CXCL)11, IL-33, TNF-beta and CD5 were suggestively associated with the risk of AD (odds ratio, OR: 1.202, 95% CI: 1.018-1.422, p = 0.030; OR: 1.029, 95% CI: 1.029-1.157, p = 0.004; OR: 1.159, 95% CI: 1.018-1.320, p = 0.026; OR: 1.111, 95% CI: 1.016-1.214, p = 0.020; OR: 0.878, 95% CI: 0.783-0.984, p = 0.025; OR: 0.809, 95% CI: 0.661-0.991, p = 0.041; OR: 0.945, 95% CI: 0.896-0.997, p = 0.038; OR: 0.764, 95% CI: 0.652-0.895, p = 8.26e-04). In addition, levels of cytokines including Axin-1, CXCL5, CXCL10, Oncostatin-M (OSM), Sulfotransferase 1A1 (SULT1A1) and TNFSF14 were suggested to be consequences of AD (Beta: -0.080, p = 0.016; Beta: -0.062, p = 0.036; Beta: -0.066, p = 0.049; Beta: -0.073, p = 0.013; Beta: -0.089, p = 0.008; Beta: -0.079, p = 0.031). IL-13, IL-18R1, TNFSF14, and TRANCE were upregulated in both lesional skin biopsies and PBMCs from AD patients.ConclusionThe study indicates that several cytokines, including IL-13, IL-18R1, TNFSF14, TRANCE, CXCL11, IL-33, TNF-beta, and CD5, are upstream of AD development, whereas a few circulating cytokines are potentially downstream in the development of AD.

Dataset Information

The causal effect of atopic dermatitis on lung cancer: A Mendelian randomization study.

Background

Materials and methods

Results

Conclusion

Publications

The causal effect of atopic dermatitis on lung cancer: A Mendelian randomization study.

Similar Datasets

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