Taylor Nicholas J, Busam Klaus J, From Lynn, Groben Pamela A, Anton-Culver Hoda, Cust Anne E, Begg Colin B, Dwyer Terence, Gallagher Richard P, Gruber Stephen B, Orlow Irene, Rosso Stefano, Thomas Nancy E, Zanetti Roberto, Rebbeck Timothy R, Berwick Marianne, Kanetsky Peter A
Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida, United States of America.
Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, New York, United States of America.
PLoS One. 2015 Mar 19;10(3):e0119920. doi: 10.1371/journal.pone.0119920. eCollection 2015.
Variation in the melanocortin-1receptor (MC1R) gene is associated with pigmentary phenotypes and risk of malignant melanoma. Few studies have reported on MC1R variation with respect to tumor characteristics, especially clinically important prognostic features. We examined associations between MC1R variants and histopathological melanoma characteristics. Study participants were enrolled from nine geographic regions in Australia, Canada, Italy and the United States and were genotyped for MC1R variants classified as high-risk [R] (D84E, R142H, R151C, R160W, and D294H, all nonsense and insertion/deletion) or low-risk [r] (all other nonsynonymous) variants. Tissue was available for 2,160 white participants of the Genes, Environment and Melanoma (GEM) Study with a first incident primary melanoma diagnosis, and underwent centralized pathologic review. No statistically significant associations were observed between MC1R variants and AJCC established prognostic tumor characteristics: Breslow thickness, presence of mitoses or presence of ulceration. However, MC1R was significantly associated with anatomic site of melanoma (p = 0.002) and a positive association was observed between carriage of more than one [R] variant and melanomas arising on the arms (OR = 2.39; 95% CI: 1.40, 4.09). We also observed statistically significant differences between sun-sensitive and sun-resistant individuals with respect to associations between MC1R genotype and AJCC prognostic tumor characteristics. Our results suggest inherited variation in MC1R may play an influential role in anatomic site presentation of melanomas and may differ with respect to skin pigmentation phenotype.
黑皮质素-1受体（MC1R）基因的变异与色素沉着表型及恶性黑色素瘤风险相关。关于MC1R变异与肿瘤特征，尤其是具有临床重要意义的预后特征的研究报道较少。我们研究了MC1R变异与黑色素瘤组织病理学特征之间的关联。研究参与者来自澳大利亚、加拿大、意大利和美国的九个地理区域，对分类为高风险[R]（D84E、R142H、R151C、R160W和D294H，均为无义突变和插入/缺失）或低风险[r]（所有其他非同义突变）的MC1R变异进行基因分型。基因、环境与黑色素瘤（GEM）研究中有2160名首次诊断为原发性黑色素瘤的白人参与者的组织可供使用，并接受了集中病理检查。未观察到MC1R变异与美国癌症联合委员会（AJCC）确定的预后肿瘤特征（Breslow厚度、有丝分裂情况或溃疡情况）之间存在统计学显著关联。然而，MC1R与黑色素瘤的解剖部位显著相关（p = 0.002），并且观察到携带一种以上[R]变异与手臂上发生的黑色素瘤之间存在正相关（OR = 2.39；95% CI：1.40，4.09）。我们还观察到，在MC1R基因型与AJCC预后肿瘤特征之间的关联方面，对阳光敏感和抗晒个体之间存在统计学显著差异。我们的结果表明，MC1R的遗传变异可能在黑色素瘤的解剖部位表现中起重要作用，并且可能因皮肤色素沉着表型而异。
