p53密码子72多态性与黑皮质素1受体变体在晒黑反应和皮肤黑色素瘤风险上的相互作用。
Interaction between p53 codon 72 polymorphism and melanocortin 1 receptor variants on suntan response and cutaneous melanoma risk.
作者信息
Nan H, Qureshi A A, Hunter D J, Han J
机构信息
Department of Epidemiology, Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, 677 Huntington Ave, Boston, MA 02115, USA.
出版信息
Br J Dermatol. 2008 Aug;159(2):314-21. doi: 10.1111/j.1365-2133.2008.08624.x. Epub 2008 May 28.
BACKGROUND
Ultraviolet (UV) radiation-induced p53 activation promotes cutaneous pigmentation by increasing transcriptional activity of pro-opiomelanocortin (POMC) in the skin. Induction of POMC/alpha-melanocyte-stimulating hormone (alpha-MSH) activates the melanocortin 1 receptor (MC1R), resulting in skin pigmentation. The common p53 codon 72 polymorphism alters the protein's transcriptional activity, which may influence the UV radiation-induced tanning response.
OBJECTIVES
We assessed the association of the p53 codon 72 polymorphism with tanning response, and its interaction with MC1R variants on tanning response and skin cancer risk.
METHODS
The assessment was done in a nested case-control study within the Nurses' Health Study [219 melanoma cases, 286 squamous cell carcinoma (SCC) cases, 300 basal cell carcinoma (BCC) cases and 874 controls], and among controls from four nested case-control studies within the Nurses' Health Study.
RESULTS
We found that the p53 Proline (Pro) allele was positively associated with childhood tanning response only among black/dark brown-haired women. Compared with the Arginine/Arginine (Arg/Arg) genotype, odds ratios (ORs) of childhood tanning tendency for Arg/Pro and Pro/Pro genotypes were 1.59 (95% CI, 0.96-2.65) and 1.56 (95% CI, 0.55-4.40), respectively. The association between MC1R variants and childhood tanning tendency was similar in both p53 Arg/Arg genotype and Pro allele carriers (Arg/Pro or Pro/Pro). The association of the p53 Pro/Pro genotype with melanoma risk was strongest among women with light pigmentation, and with MC1R variants, with the joint risk categories having the highest overall risk. We did not observe such interaction for SCC and BCC.
CONCLUSIONS
Our study suggests the involvement of the p53 codon 72 polymorphism in the skin tanning response and potential interaction with skin pigmentation on melanoma risk. Further work is needed to evaluate the association between p53 and its associated proteins and skin cancer risk.
背景
紫外线（UV）辐射诱导的p53激活通过增加皮肤中阿片促黑素皮质素原（POMC）的转录活性来促进皮肤色素沉着。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。常见的p53密码子72多态性改变了该蛋白的转录活性，这可能会影响紫外线辐射诱导的晒黑反应。
目的
我们评估了p53密码子72多态性与晒黑反应的关联，以及它与MC1R变体在晒黑反应和皮肤癌风险方面的相互作用。
方法
该评估在护士健康研究中的一项巢式病例对照研究中进行[219例黑色素瘤病例、286例鳞状细胞癌（SCC）病例、300例基底细胞癌（BCC）病例和874例对照]，并在护士健康研究中的四项巢式病例对照研究的对照中进行。
结果
我们发现，仅在黑色/深棕色头发的女性中，p53脯氨酸（Pro）等位基因与儿童晒黑反应呈正相关。与精氨酸/精氨酸（Arg/Arg）基因型相比，Arg/Pro和Pro/Pro基因型的儿童晒黑倾向的比值比（OR）分别为1.59（95%CI，0.96 - 2.65）和1.56（95%CI，0.55 - 4.40）。在p53 Arg/Arg基因型和Pro等位基因携带者（Arg/Pro或Pro/Pro）中，MC1R变体与儿童晒黑倾向之间的关联相似。p53 Pro/Pro基因型与黑色素瘤风险的关联在色素沉着浅的女性中最强，并且与MC1R变体相关，联合风险类别具有最高的总体风险。我们在SCC和BCC中未观察到这种相互作用。
结论
我们的研究表明p53密码子72多态性参与皮肤晒黑反应，并在黑色素瘤风险方面与皮肤色素沉着存在潜在相互作用。需要进一步的研究来评估p53及其相关蛋白与皮肤癌风险之间的关联。
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