Impact of 26 Skin Diseases on the Risk of Non-Small Cell Lung Cancer: A Mendelian Randomization Study Using FinnGen R11 Data

Purpose To determine whether genetic predisposition to various skin diseases influences the risk of non-small cell lung cancer (NSCLC) through Mendelian randomization (MR).

Single nucleotide polymorphisms (SNPs) associated with 26 skin diseases were extracted from the FinnGen R11 dataset and underwent rigorous quality control. To evaluate the association between these skin diseases and the risk of non-small cell lung cancer (NSCLC), we applied several analytical methods, including inverse-variance weighted (IVW), MR-Egger regression, weighted median, Simple mode, and Weighted mode. The robustness of the findings was further supported by assessing SNP heterogeneity with the Cochran Q test and evaluating horizontal pleiotropy using the MR-Egger intercept test.

Our study revealed that genetically predicted dermatitis herpetiformis (DH) was significantly associated with an elevated risk of squamous cell carcinoma of the lung (SCC). Acne was nominally linked to an increased risk of SCC. Additionally, rhinophyma (RHN), hidradenitis suppurativa (HS), and DH were nominally associated with a higher risk of adenocarcinoma of the lung (ADC). Of the remaining 22 skin diseases analyzed, 7 lacked sufficient instrumental variables to meet inclusion criteria. The other 15 skin diseases showed no statistically significant association with NSCLC.

This study ultimately analyzed the relationship between 19 skin diseases and NSCLC at the genetic level, while 7 other skin diseases could not be analyzed due to insufficient instrumental variables. Dermatitis herpetiformis and acne were associated with an increased risk of squamous cell carcinoma of the lung. Additionally, rhinophyma, hidradenitis suppurativa, and dermatitis herpetiformis were associated with an increased risk of adenocarcinoma of the lung. Competing Interest Statement The authors have declared no competing interest. Funding Statement Yes Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Not Applicable The details of the IRB/oversight body that provided approval or exemption for the research described are given below: N/A I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Not Applicable I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Not Applicable I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Not Applicable Data Availability The dataset in this study can be found in the FinnGen database.