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Updated: May 31, 2026
Pharmacologic Induction of Epidermal Melanin and Protection Against Sunburn in a Humanized Mouse Model
Published on: September 7, 2013
Genetic determinants of UV-susceptibility in non-melanoma skin cancer
Marleen M Welsh1, Margaret R Karagas, Jacquelyn K Kuriger
1Department of Preventive Medicine and Biometrics, Uniformed Services University of the Health Sciences, Bethesda, Maryland, United States of America.
Abstract:
A milieu of cytokines and signaling molecules are involved in the induction of UV-induced immune suppression and thus the etiology of non-melanoma skin cancer (NMSC). Targeting the UV-induced immunosuppression pathway, and using a large population based study of NMSC, we have investigated the risk associated with functional variants in 10 genes (IL10, IL4, IL4R, TNF, TNFR2, HTR2A, HRH2, IL12B, PTGS2, and HAL). The most prominent single genetic effect was observed for IL10. There was increasing risk for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with increasing number of variant IL10 haplotypes (BCC: p(trend) = 0.0048; SCC: p(trend) = 0.031). Having two IL10 GC haplotypes was associated with increased odds ratios of BCC and SCC (OR(BCC) = 1.5, 95% CI 1.1-1.9; OR(SCC) = 1.4, 95% CI 1.0-1.9), and these associations were largely confined to women (OR(BCC) = 2.2, 95% CI 1.4-3.4; SCC: OR(SCC) = 1.8, 95% CI 1.1-3.0). To examine how combinations of these variants contribute to risk of BCC and SCC, we used multifactor dimensionality reduction (MDR) and classification and regression trees (CART). Results from both of these methods found that in men, a combination of skin type, burns, IL10, IL4R, and possibly TNFR2 were important in both BCC and SCC. In women, skin type, burns, and IL10 were the most critical risk factors in SCC, with risk of BCC involving these same factors plus genetic variants in HTR2A, IL12B and IL4R. These data suggest differential genetic susceptibility to UV-induced immune suppression and skin cancer risk by gender.
Insights
Genetic variants in the IL10 gene increase the risk of non-melanoma skin cancer (NMSC), particularly in women. Combinations of genetic and environmental factors influence NMSC development differently between genders.
Area of Science:
- Immunology
- Genetics
- Dermatology
Background:
- UV radiation induces immune suppression, contributing to non-melanoma skin cancer (NMSC).
- Cytokines and signaling molecules play a role in UV-induced immunosuppression and NMSC etiology.
- Investigating genetic variants in immune-related genes can elucidate NMSC risk factors.
Purpose of the Study:
- To investigate the risk associated with functional variants in 10 immune-related genes in NMSC.
- To identify specific genetic contributions to UV-induced immune suppression and skin cancer.
- To explore gender-specific differences in genetic susceptibility to NMSC.
Main Methods:
- A large population-based study of NMSC was conducted.
- Functional variants in 10 genes (IL10, IL4, IL4R, TNF, TNFR2, HTR2A, HRH2, IL12B, PTGS2, HAL) were analyzed.
- Multifactor dimensionality reduction (MDR) and classification and regression trees (CART) were used to analyze gene combinations.
Main Results:
- The IL10 gene showed the most significant association with NMSC risk.
- Increasing numbers of variant IL10 haplotypes correlated with increased risk of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
- Gender-specific risk factors were identified: IL10 variants posed higher risks for women, while combined genetic and environmental factors influenced risk differently in men and women.
Conclusions:
- Genetic variants, particularly in IL10, contribute to UV-induced immune suppression and NMSC risk.
- Gender plays a significant role in susceptibility to NMSC, with distinct genetic and environmental risk factor combinations.
- Targeting the UV-induced immunosuppression pathway offers potential for NMSC prevention strategies.
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