Genetic factors underlying basal cell carcinoma risk: a narrative review

Sitong Ju, Wanlin Fan, Alexander C. Rokohl, Yongwei Guo, Vinodh Kakkassery, Ludwig M. Heindl*

*Corresponding author for this work
1 Citation (Scopus)


Background and Objective: Basal cell carcinoma (BCC) is the most common type of malignant tumor and a subtype of non-melanoma skin cancer (NMSC). It has a slow progression, metastasizes extremely rarely, but sometimes causes severe local tissue destruction. The constantly increasing incidence of BCC results from a complex interaction between environmental, genetic, and other risk factors. Several oncogenes and antioncogenes have been proved to be involved in BCC pathogenesis, including the vital effector portions of the hedgehog (HH) signaling pathway (i.e., PTCH1, PTCH2, SMO or SUFU genes), MC1R, and TP53. HH signaling pathway dysregulation is related to dysplasia and carcinoma, including Gorlin syndrome (GS) and sporadic cancers. Mutations caused by ultraviolet (UV) light and/or copy-loss heterozygosity of related genes lead to the abnormal signaling pathway activation, responsible for over 90% of the BCC cases. This review intends to provide a revision of the genetic factors affecting BCC. Methods: The PubMed database was searched with a search algorithm [(basal cell carcinoma) OR (BCC)] AND [(gene) OR (pathway)], till May 2021, to filter out relevant publications. Relevant researches omitted from this search algorithm were also selected from the specific full-text papers reference lists. No language restrictions included in our search. Key Content and Findings: This review provides a revision of several potential mechanisms that may involve in BCC carcinogenesis. Some genetic agents have been considered the risk factors for BCC, including the vital effector portions of the HH signaling pathway, MC1R, and TP53. Certain inherited disorders, including Gorlin syndrome, xeroderma pigmentosum, and Bazex-Dupré-Christol syndrome, are considered genetic risk factors for BCC, predisposing BCC at an early age. Other genes, such as BRCA1, BRCA2, CTLA-4, AS3MT, N-Myc and Hippo-YAP pathway target genes (MYCN PTPN14, PPP6C, STK19, LATS1) also show the potential relevance in BCC tumorigenesis and progression. Conclusions: The hereditary basis of BCCs can vary from targeted mutations in the HH signaling pathway to deficiencies of tumor suppressors and melanin synthesis. These may lead to DNA damage and promotes BCC growth. The knowledge and characterization of the BCC genetic factors could underlie the development of new therapies.

Original languageEnglish
Article number20
JournalFrontiers of Oral and Maxillofacial Medicine
Publication statusPublished - 10.06.2023

Research Areas and Centers

  • Research Area: Luebeck Integrated Oncology Network (LION)
  • Centers: University Cancer Center Schleswig-Holstein (UCCSH)

DFG Research Classification Scheme

  • 205-14 Haematology, Oncology
  • 206-11 Ophthalmology

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