Abstract
Background
Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic reviews and meta-analyses have found that AD is associated with cancer risk at several sites; if found to be causal this could highlight potential treatment targets to reduce cancer risk.
Objectives
To assess the potential causative link between AD and 14 site-specific cancers in a two-sample randomization study.
Methods
From the largest genome-wide association study (GWAS) of AD (10,788 cases and 30,047 non-cases), genetic variants highly associated (p < 5 × 10−8) with AD in the European population were selected as instrumental variables (IVs). Data from large cancer consortia, as well as the UK Biobank study (n = 442,239) and the FinnGen study (n = 218,792), were employed to assess genetic associations with 14 site-specific cancers and overall cancer. A set of complementary approaches and sensitivity analyses were carried out to examine the robustness of our results. In addition, associations for the same cancer site from different data sources were combined using meta-analyses.
Results
We discovered no strong causal evidence of AD on the risk of overall cancer, with effect estimates close to zero. After the Benjamini–Hochberg correction, the inverse-variance weighted method indicated no association between AD and overall cancer risk in both the UK Biobank (OR, 1.00; 95% CI, 0.94–1.06; FDR, 0.98) and FinnGen studies (OR, 0.96; 95% CI, 0.92–1.02; FDR, 0.68). No strong evidence of an association was found between genetically predicted AD and the risk of any site-specific cancers.
Conclusions
Our MR investigation does not support a causal effect of AD on cancer risk. This finding has important implications for the prevention and management of both AD and cancer, as it reduces the concern of potential adverse effects of AD on cancer outcomes.
Atopic dermatitis (AD) accounts for a large proportion of the burden of skin disease, with a prevalence of around 10% among adults worldwide. In addition, systematic reviews and meta-analyses have found that AD is associated with cancer risk at several sites; if found to be causal this could highlight potential treatment targets to reduce cancer risk.
Objectives
To assess the potential causative link between AD and 14 site-specific cancers in a two-sample randomization study.
Methods
From the largest genome-wide association study (GWAS) of AD (10,788 cases and 30,047 non-cases), genetic variants highly associated (p < 5 × 10−8) with AD in the European population were selected as instrumental variables (IVs). Data from large cancer consortia, as well as the UK Biobank study (n = 442,239) and the FinnGen study (n = 218,792), were employed to assess genetic associations with 14 site-specific cancers and overall cancer. A set of complementary approaches and sensitivity analyses were carried out to examine the robustness of our results. In addition, associations for the same cancer site from different data sources were combined using meta-analyses.
Results
We discovered no strong causal evidence of AD on the risk of overall cancer, with effect estimates close to zero. After the Benjamini–Hochberg correction, the inverse-variance weighted method indicated no association between AD and overall cancer risk in both the UK Biobank (OR, 1.00; 95% CI, 0.94–1.06; FDR, 0.98) and FinnGen studies (OR, 0.96; 95% CI, 0.92–1.02; FDR, 0.68). No strong evidence of an association was found between genetically predicted AD and the risk of any site-specific cancers.
Conclusions
Our MR investigation does not support a causal effect of AD on cancer risk. This finding has important implications for the prevention and management of both AD and cancer, as it reduces the concern of potential adverse effects of AD on cancer outcomes.
| Original language | English |
|---|---|
| Pages (from-to) | 2490-2497 |
| Number of pages | 8 |
| Journal | Journal of the European Academy of Dermatology and Venereology |
| Volume | 37 |
| Issue number | 12 |
| Early online date | 21 Jul 2023 |
| DOIs | |
| Publication status | Published - 1 Dec 2023 |
Bibliographical note
Funding Information:Xiangyu Wang is funded by the National Natural Science Foundation of China (No. 82102887). Jing Wang is funded by the China National Key R&D (or Research and Development) Program (No. 2020AAA0105000 and 2020AAA0105004) and the National Natural Science Foundation of China (No. 82173328). The funders had no role in the study design, data collection and analysis, decision to publish or the preparation of the manuscript.
Funding Information:
The authors would like to thank the participants of the individual studies contributing to the FinnGen, UK Biobank, Breast Cancer Association Consortium, the Ovarian Cancer Association Consortium, International Lung Cancer Consortium and the Prostate Cancer Association Group to Investigate Cancer Associated Alterations in the Genome consortium.
Publisher Copyright:
© 2023 European Academy of Dermatology and Venereology.
