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

Abstract

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