German Cancer Research Center DKFZ, Heidelberg, Germany.
J Dermatol Sci. 2011 Jul;63(1):47-54. doi: 10.1016/j.jdermsci.2011.03.006. Epub 2011 Apr 1.
Basal cell carcinoma (BCC) of the skin is the most common neoplasm among the Caucasian population of the western world. Ultraviolet (UV) radiation-induced p53 activation promotes cutaneous pigmentation by increasing transcriptional activity of pro-opiomelanocortin (POMC) in the skin. Induction of POMC/α-melanocyte-stimulating hormone (α-MSH) activates the melanocortin 1 receptor (MC1R), resulting in skin pigmentation. The tumor suppressor p53 is a key player in stress responses that preserve genomic stability, responding to a variety of insults including DNA damage, hypoxia, metabolic stress and oncogene activation. Malfunction of the p53 pathway is an almost universal hallmark of human tumors. Polymorphisms in the gene encoding p53 (TP53) alter its transcriptional activity, which in turn may influence the UV radiation-induced tanning response.
The aim of the present work is to test association between POMC and TP53 genetic variability, the possible interplay with host factors and the risk of basal cell carcinoma of skin.
We covered the variability of the two genes we used 17 tagging polymorphisms in 529 BCC cases and 532 healthy controls. We have also tested the possible interactions between the genetic variants and three known risk factors for BCC: skin complexion, sun effect and skin response to sun exposure.
We did not observe any statistically significant association between SNPs in these two genes and BCC risk overall, nor interactions of SNPs with known BCC risk factors. However we found that, in the group of subjects with lower sun exposure, carriers of one copy of the C allele of the TP53 SNP rs12951053 had a decreased risk of BCC (OR=0.28, 95% CI 0.12-0.62, P=0.002).
We have observed that the interplay of an environmental risk factor and one polymorphism in TP53 gene could modulate the risk of BCC.
皮肤基底细胞癌（BCC）是西方白种人群中最常见的肿瘤。紫外线（UV）辐射诱导的 p53 激活通过增加皮肤中前阿黑皮素原（POMC）的转录活性促进皮肤色素沉着。POMC/α-促黑素细胞激素（α-MSH）的诱导激活黑素皮质素 1 受体（MC1R），导致皮肤色素沉着。肿瘤抑制因子 p53 是维持基因组稳定性的应激反应的关键参与者，它可以响应各种应激，包括 DNA 损伤、缺氧、代谢应激和癌基因激活。p53 途径的功能障碍是人类肿瘤几乎普遍的特征。编码 p53（TP53）的基因中的多态性改变了其转录活性，这反过来又可能影响紫外线诱导的晒黑反应。
本研究旨在检验 POMC 和 TP53 基因多态性与皮肤基底细胞癌风险之间的关联，以及宿主因素的可能相互作用。
我们研究了这两个基因的变异性，在 529 例 BCC 病例和 532 例健康对照中使用了 17 个标签多态性。我们还测试了遗传变异与三个已知的 BCC 风险因素（皮肤肤色、阳光效应和皮肤对阳光暴露的反应）之间的可能相互作用。
我们没有观察到这两个基因的 SNP 与 BCC 风险之间存在任何统计学上的显著关联，也没有观察到 SNP 与已知的 BCC 风险因素之间的相互作用。然而，我们发现，在暴露于较低阳光的人群中，TP53 SNP rs12951053 的 C 等位基因携带者的 BCC 风险降低（OR=0.28，95%CI 0.12-0.62，P=0.002）。
我们观察到环境风险因素和 TP53 基因的一个多态性之间的相互作用可能调节 BCC 的风险。
