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Soo Park, MD
Soo Park, MD
Posted: Monday, June 27, 2022
Given that sonic Hedgehog pathway dysregulation has been implicated in the development of basal cell carcinoma, Astrid J. Rodriguez-Acevedo, PhD, of the University of Queensland’s Dermatology Research Centre, Brisbane, Australia, and colleagues investigated a possible wider role of sonic Hedgehog gene variants in skin carcinogenesis. Using a cohort of 795 unrelated Australian adults with available blood samples—across a 25-year time frame—they conducted a prospective study to assess associations of genes in the sonic Hedgehog pathway with lifetime development of any keratinocyte cancer and with developing either basal cell carcinomas or squamous cell carcinomas exclusively.
The investigators turned up some genetic suspects, they wrote in BMC Cancer. “We found associations between single nucleotide polymorphism rs4848627 (GLI2), [which is] related to DNA synthesis in keratinocytes, and [the] development of any keratinocyte cancer (P < .01),” they stated. They also noted that rs4848627 was shown to be related to the development of squamous cell carcinomas exclusively (P < .01), doubling the risk of these cancers. The GLI2 gene “contained the most single nucleotide polymorphisms statistically significantly associated with any keratinocyte cancer, as well as with exclusive development of basal cell carcinomas or squamous cell carcinoma,” the team revealed.
Further, single nucleotide polymorphism rs3217882, located in CCND2, was associated with basal cell carcinoma development exclusively (P < .01). An association of PRKACG (protein kinase cAMP‐activated catalytic subunit gamma) with any keratinocyte cancer (P = .013) was also suggested.
Many skin cancer genes have been associated with both basal cell and squamous cell carcinomas, but the authors said no prior human studies had evaluated whether genes involved in the sonic Hedgehog pathway affect the risk of development of either type of skin cancer alone. In total, the team genotyped 311 cases with any keratinocyte cancer (186 developing basal cell carcinomas alone, 55 developing squamous cell carcinomas alone, and 70 developing both) and 484 controls, comparing allele frequencies of 158 independent single nucleotide polymorphisms across 43 sonic Hedgehog genes between the cases and controls.
Disclosure: The study authors reported no conflicts of interest.
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