Genetic Determinants of UV-Susceptibility in Non-Melanoma Skin Cancer
Menée sur 2 493 participants de la cohorte "New Hampshire Health Study" (852 témoins, 931 cas de carcinomes à cellules basales et 710 cas de carcinomes épidermoïdes), cette étude identifie des déterminants génétiques d'une susceptibilité à la suppression immunitaire induite par une exposition aux rayonnements ultra-violets
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 (<italic>IL10</italic>, <italic>IL4</italic>, <italic>IL4R</italic>, <italic>TNF</italic>, <italic>TNFR2</italic>, <italic>HTR2A</italic>, <italic>HRH2</italic>, <italic>IL12B</italic>, <italic>PTGS2</italic>, and <italic>HAL</italic>). The most prominent single genetic effect was observed for <italic>IL10</italic>. There was increasing risk for both basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) with increasing number of variant <italic>IL10</italic> haplotypes (BCC: p<sub>trend</sub> = 0.0048; SCC: p<sub>trend</sub> = 0.031). Having two <italic>IL10</italic> GC haplotypes was associated with increased odds ratios of BCC and SCC (OR<sub>BCC</sub> = 1.5, 95% CI 1.1–1.9; OR<sub>SCC</sub> = 1.4, 95% CI 1.0–1.9), and these associations were largely confined to women (OR<sub>BCC</sub> = 2.2, 95% CI 1.4–3.4; SCC: OR<sub>SCC</sub> = 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, <italic>IL10</italic>, <italic>IL4R</italic>, and possibly <italic>TNFR2</italic> were important in both BCC and SCC. In women, skin type, burns, and <italic>IL10</italic> were the most critical risk factors in SCC, with risk of BCC involving these same factors plus genetic variants in <italic>HTR2A</italic>, <italic>IL12B</italic> and <italic>IL4R</italic>. These data suggest differential genetic susceptibility to UV-induced immune suppression and skin cancer risk by gender.</p>
PLOS ONE 2011