Susceptibility Loci-Associated Cutaneous Squamous Cell Carcinoma Invasiveness

Abstract

Genome-wide association studies have identified genetic loci associated with cutaneous squamous cell carcinoma (cSCC) risk, but single-nucleotide polymorphism associations with cSCC invasiveness have not been investigated. We examined associations between cSCC invasiveness and 23 reported single-nucleotide polymorphisms among 67,833 non-Hispanic white subjects. Additionally, we performed a genome-wide scan and identified one SNP with significantly different frequencies in 5,724 subjects with at least one invasive tumor and 1,943 subjects with in situ tumors only. We then compared genotype frequencies among the invasive and in situ groups with those of 60,166 control subjects. The genome-wide scan identified that the T allele in single-nucleotide polymorphism rs41269979 in the class II human leukocyte antigen region was more frequent in the invasive than the in situ group (P = 4.93 × 10). Single-nucleotide polymorphisms in five of the 23 previously associated loci showed odds ratio heterogeneity between the in situ and invasive groups: rs447510 in HLA-DQA1 (P = 2.93 × 10), rs12203592 in IRF4 (P = 3.94 × 10), rs1805007 in MC1R (P = 7.71 × 10), and two SNPs in DEF8 (rs4268748, P = 1.09 × 10 and rs8063761, P = 1.40 × 10). These findings may provide new insight into the genetic basis of cSCC invasiveness and may help identify individuals at higher risk for developing clinically aggressive cSCC.

Clinical features and outcome of dermal squamous cell carcinoma in 193 dogs (1987‐2017)

“…8,13,20,21 Apart from solar UV exposure, other risk factors for development of dermal SCC identified in people include prior trauma, immunosuppression, papilloma virus infection and exposure to carcinogenic chemicals such as cigarette tar. 22,23 Similar risk factors including viral infections, immunosuppression and previous trauma or burns to the region have been suggested in veterinary species. [24][25][26][27][28] A gold standard treatment approach has not been established for canine dermal SCC, however, some methods have been extrapolated from SCC in other locations and species.…”

“…Apart from solar UV exposure, other risk factors for development of dermal SCC identified in people include prior trauma, immunosuppression, papilloma virus infection and exposure to carcinogenic chemicals such as cigarette tar . Similar risk factors including viral infections, immunosuppression and previous trauma or burns to the region have been suggested in veterinary species …”

Case report of a 65-year-old man with biatrial metastatic localisation from poorly differentiated cutaneous squamous cell carcinoma

“…Cutaneous squamous cell carcinoma (cSCC) is the second most common form of nonmelanoma skin cancer after basal cell carcinoma. [1] Its origin is the malignant proliferation of epidermal keratinocytes due to multiple biological events [2,3]. Previously reported findings showed how immunosuppressed patients tend to develop multiple and more aggressive skin cancer.…”

A Review of the Literature of Surgical and Nonsurgical Treatments of Invasive Squamous Cells Carcinoma

“…cSCC arises frequently in field of cancerization rather than de novo. Genetic alterations are recognizable both in tumoral cells and in elements without histological atypia, so microenvironment of premalignant lesions can influence their progression to invasive and metastatic cSCC [ 5 , 6 ]. The genetic background also influences malignant potential of cSCC, as Genome-wide association studies (GWAS) have identified genetic loci associated with cSCC risk, and single nucleotide polymorphisms (SNP) of the class II human leukocyte antigen region associations with tumor development have recently been investigated [ 6 ].…”

“…cSCC results from the malignant proliferation of epidermal keratinocytes due to complex biological events involving multiple factors [ 5 , 6 ]. Ultraviolet radiations (UVs), particularly UVB (290–320 nm) and UVA (320–340 nm) radiations, have a pivotal role in tumor pathogenesis.…”