A multi-phenotype analysis reveals 19 susceptibility loci for basal cell carcinoma and 15 for squamous cell carcinoma.
Mathias SeviiriMatthew H LawJue-Sheng OngPuya GharahkhaniPierre Fontanillasnull nullCatherine M OlsenDavid C WhitemanStuart MacgregorPublished in: Nature communications (2022)
Basal cell carcinoma and squamous cell carcinoma are the most common skin cancers, and have genetic overlap with melanoma, pigmentation traits, autoimmune diseases, and blood biochemistry biomarkers. In this multi-trait genetic analysis of over 300,000 participants from Europe, Australia and the United States, we reveal 78 risk loci for basal cell carcinoma (19 previously unknown and replicated) and 69 for squamous cell carcinoma (15 previously unknown and replicated). The previously unknown risk loci are implicated in cancer development and progression (e.g. CDKL1), pigmentation (e.g. TPCN2), cardiometabolic (e.g. FADS2), and immune-regulatory pathways for innate immunity (e.g. IFIH1), and HIV-1 viral load modulation (e.g. CCR5). We also report an optimised polygenic risk score for effective risk stratification for keratinocyte cancer in the Canadian Longitudinal Study of Aging (794 cases and 18139 controls), which could facilitate skin cancer surveillance e.g. in high risk subpopulations such as transplantees.
Keyphrases
- basal cell carcinoma
- genome wide
- squamous cell carcinoma
- dna methylation
- papillary thyroid
- lymph node metastasis
- skin cancer
- copy number
- squamous cell
- locally advanced
- genome wide association study
- public health
- human immunodeficiency virus
- gene expression
- hiv infected
- antiretroviral therapy
- hiv positive
- childhood cancer
- dendritic cells
- transcription factor
- hiv aids
- hiv testing
- radiation therapy