Abstract
A single nucleotide polymorphism (SNP) 35 kb upstream of the HLA-C gene is associated with HLA-C expression, and the high expressing genotype (CC) has been associated with HIV-I control. HLA-C is unique among the classical MHC class I molecules for its role in the control of viral infections and recognition of abnormal or missing self. This immunosurveillance is central to the pathogenesis of non-melanoma skin cancer (NMSC), and of squamous cell carcinoma (SCC) in particular. While sun exposure is a major risk factor for these cancers, cutaneous infections with genus β-HPV have been implicated in the development of SCC. We hypothesized that the high expression HLA-C genotype is associated with β-HPV infections. Therefore, we investigated the association between β-HPV serology and the −35 kb SNP (rs9264942) in a population-based case-control study of 510 SCC cases and 608 controls. Among controls, the high expression −35 kb SNP genotype (CC) reduced the likelihood of positive serology for multiple (≥2) β-HPV infections (OR = 0.49, 95% CI: 0.25–0.97), and β-HPV species 2 infection (OR = 0.43, 95% CI: 0.23–0.79). However, no association with β-HPV status was observed among SCC cases. Our findings suggest that underlying immunogenotype plays an important role in differential control of β-HPV in SCC cases and controls.
Highlights
Non-melanoma skin cancers (NMSC) represent the most common malignancies in the world with increasing incidence rates [1,2]
We examined the association of the 235 kb single nucleotide polymorphism (SNP) genotype with beta human papilloma viruses (b-HPV) status among squamous cell carcinoma (SCC) cases and controls, comparing those with no antibody positivity for b-HPV to those with any positivity, and individuals with multiple b-HPV types (Table 2)
The high expression 235 kb SNP genotype (CC) reduced the likelihood of positive serology for multiple ($2) b-HPV infections (OR = 0.49, 95% confidence intervals (95% CI): 0.25–0.97)
Summary
Non-melanoma skin cancers (NMSC) represent the most common malignancies in the world with increasing incidence rates [1,2]. Like the NK cells, cd T cells exhibit rapid response to antigens, stress-associated factors such as heat shock proteins, and express activating natural killer group 2 member D (NKG2D) receptors which respond to tumor or virally induced MHC I chain-related stress proteins MICA and MICB [12,13]. Deregulation of the innate and T cell-mediated immune responses are implicated in a number of autoimmune disorders and skin pathologies [6,14,15]. This includes the rare genetic disorder Epidermodysplasia Verruciformis (EV) that is associated with extreme susceptibility to persistent b-HPV infections and increased SCC risk [4,16]
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