Genetic determinants of UV-susceptibility in non-melanoma skin cancer.
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 a...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2011-01-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3132750?pdf=render |
| _version_ | 1817982888388329472 |
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| author | Marleen M Welsh Margaret R Karagas Jacquelyn K Kuriger Andres Houseman Steven K Spencer Ann E Perry Heather H Nelson |
| author_facet | Marleen M Welsh Margaret R Karagas Jacquelyn K Kuriger Andres Houseman Steven K Spencer Ann E Perry Heather H Nelson |
| author_sort | Marleen M Welsh |
| collection | DOAJ |
| description | 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. |
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| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-13T23:26:56Z |
| publishDate | 2011-01-01 |
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| series | PLoS ONE |
| spelling | doaj.art-4781c04809de4800a40dfa34792ffef82022-12-22T02:25:02ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-01-0167e2001910.1371/journal.pone.0020019Genetic determinants of UV-susceptibility in non-melanoma skin cancer.Marleen M WelshMargaret R KaragasJacquelyn K KurigerAndres HousemanSteven K SpencerAnn E PerryHeather H NelsonA 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.http://europepmc.org/articles/PMC3132750?pdf=render |
| spellingShingle | Marleen M Welsh Margaret R Karagas Jacquelyn K Kuriger Andres Houseman Steven K Spencer Ann E Perry Heather H Nelson Genetic determinants of UV-susceptibility in non-melanoma skin cancer. PLoS ONE |
| title | Genetic determinants of UV-susceptibility in non-melanoma skin cancer. |
| title_full | Genetic determinants of UV-susceptibility in non-melanoma skin cancer. |
| title_fullStr | Genetic determinants of UV-susceptibility in non-melanoma skin cancer. |
| title_full_unstemmed | Genetic determinants of UV-susceptibility in non-melanoma skin cancer. |
| title_short | Genetic determinants of UV-susceptibility in non-melanoma skin cancer. |
| title_sort | genetic determinants of uv susceptibility in non melanoma skin cancer |
| url | http://europepmc.org/articles/PMC3132750?pdf=render |
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