Causal Relationship and Potential Common Pathogenic Mechanisms Between Alopecia Areata and Related Cancer

Zexin Zhu,1 Xiaoxue Wang2 1Department of Surgical Oncology, the Comprehensive Breast Care Center, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Dermatology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Xiaoxue Wang, Department of Dermatology, the Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China, Email [email protected]: Alopecia areata (AA) is an autoimmune skin disease. Observational studies have reported an association between AA and cancer. However, the causal relationship between AA and cancer has not been reported. We employed a two-sample Mendelian randomization (MR) study to assess the causality between AA and 17 subtypes of cancers.Methods: We employed a two-sample Mendelian randomization (MR) study to assess the causality between AA and 17 subtypes of cancers. AA and cancers’ association genome-wide association study (GWAS) data were collected. The inverse variance weighted (IVW) method was utilized as the principal method in our Mendelian randomization (MR) study, with additional use of the MR-Egger, weighted median, simple mode, and weighted mode methods. After that, we explored the underlying biological mechanisms by Bioinformatic Analysis.Results: According to our MR analysis, AA has a causal relationship with hepatic bile duct cancer (HBDC, (odds ratio [OR] = 0.944, 95% confidence interval [CI] = 0.896– 0.994, P-value = 0.030) and colorectal cancer (CRC, OR = 0.981, 95% CI = 0.963– 0.999, P-value = 0.046). AA could decrease the risk of HBDC and CRC. No causal link between AA and other subtypes of cancers was observed. No heterogeneity or pleiotropy was observed. Furthermore, disease-related genes were obtained, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis results showed that the set of genes associated with immunity-inflammatory signaling pathway.Conclusion: This study provided new evidence of the relationship between AA with HBDC and CRC. AA may play a protective role in both HBDC and CRC progression. This could provide newer avenues for research in search of treatment for HBDC and CRC.Keywords: alopecia areata, cancer, causal relationship, colorectal cancer, hepatic bile duct cancer, Mendelian randomization