Background:Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasia characterized by lesions including pathogenic CD207+ dendritic cells among an inflammatory infiltrate with recurrent, mutually exclusive somatic activating mutations in MAPKpathway genes in ~85% of LCH lesions. Our group and others have reported that Hispanic populations are more likely to develop LCH, particularly high-risk LCH, than non-Hispanic counterparts. Our group previously identified and validated a risk SNP in SMAD6associated with a 3-fold increase in LCH risk that was also enriched in those of Hispanic ancestry; however, germline risk factors have yet to be fully elucidated in the higher-risk Hispanic population.