Interaction between p53 codon 72 polymorphism and melanocortin 1 receptor variants on suntan response and cutaneous melanoma risk.
Interaction between p53 codon 72 polymorphism and melanocortin 1 receptor variants on suntan response and cutaneous melanoma risk.
复制标题
p53 密码子 72 多态性和黑皮质素 1 受体变异之间的相互作用对晒黑反应和皮肤黑色素瘤风险的影响。
DOI：
10.1111/j.1365-2133.2008.08624.x
复制
发表时间：
2008
期刊：
影响因子：
--
通讯作者：
Han,J
中科院分区：
文献类型：
--
作者：
Nan,H;Qureshi,AA;Hunter,DJ;Han,J
背景紫外线(UV)辐射诱导的P53活化通过增加皮肤中前阿片黑素皮质素(POMC)的转录活性来促进皮肤色素沉着。诱导POMC/α-黑素细胞刺激素(α-MSH)激活黑素皮质素1受体(MC1R)，导致皮肤色素沉着。目的研究P53密码子72多态与皮肤晒黑反应的关系，以及与MC1R变异对皮肤晒黑反应和皮肤癌风险的影响。方法采用护士健康研究中的嵌套式病例对照研究[219例黑色素瘤、286例鳞状细胞癌、300例基底细胞癌和874例对照]，结果我们发现，只有在黑人或深棕色头发的女性中，P53-Pro等位基因与儿童晒黑反应呈正相关。与Arg/Arg(Arg/Arg)基因型相比，Arg/Pro和Pro/Pro基因型对儿童晒黑倾向的OR值分别为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变异与儿童晒黑倾向的相关性相似。在轻度色素沉着的女性中，P53 Pro/Pro基因与黑色素瘤风险的关联最强，与MC1R变异体的关联最强，联合风险类别具有最高的总体风险。我们没有观察到鳞癌和鳞癌的这种相互作用。结论我们的研究表明，P53密码子72多态参与了皮肤晒黑反应，并可能与皮肤色素沉着的黑色素瘤风险相互作用。还需要进一步的工作来评估P53及其相关蛋白与皮肤癌风险之间的关联。
BackgroundUltraviolet (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 common p53 codon 72 polymorphism alters the protein’s transcriptional activity, which may influence the UV radiation‐induced tanning response.ObjectivesWe 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.MethodsThe 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.ResultsWe 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.ConclusionsOur 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.