Department of Dermatology, University of Utah Health Sciences Center, Salt Lake City, UT 84112, USA.
G Ital Dermatol Venereol. 2010 Feb;145(1):37-45.
About 5-10% of human cutaneous malignant melanoma is hereditary and known to involve rare germline mutations in highly penetrant, autosomal dominant genes. These genes are important in cell cycle control but are not responsible for all familial cases of melanoma. Epidemiologic studies have linked specific phenotypic traits including fair skin, light-colored eyes, and poor tanning ability to melanoma risks. The ability to visually discern and define pigmentary phenotypes in humans and in animal models has permitted elucidation of many genes involved in pigmentation and melanin biosynthesis. Additional genetic epidemiological studies have recently identified a subset of these pigmentation genes that are associated with risk for melanoma and other cutaneous malignancies as well as photosensitivity. Genome-wide association studies (GWAS) have unveiled single nucleotide polymorphisms (SNPs) or genetic variants in MC1R, TPCN2, ASIP, KITLG, NCKX5, TYR, IRF4, OCA2, and TYRP1 pigmentation genes. These findings emphasize the contribution of pigmentation pathways to melanoma predisposition and tumorigenesis through gene-environment interactions. Since pigmentation genes in the melanin synthesis pathway also confer risk for cutaneous malignancy, a better understanding of the operative molecular mechanisms involved in this relationship has the potential to impact individual risk assessment for cutaneous malignant melanoma in the future. This paper is an overview of our current understanding of pigmentation gene modifications that have been associated with melanoma risk and how these genes can enrich clinical management, prevention, and early detection of malignant melanoma.
约 5-10%的人类皮肤恶性黑色素瘤是遗传性的，已知涉及罕见的种系突变，这些突变存在于高外显率、常染色体显性基因中。这些基因在细胞周期控制中很重要，但并非所有家族性黑色素瘤病例的原因。流行病学研究将特定的表型特征（包括浅色皮肤、浅色眼睛和较差的晒黑能力）与黑色素瘤风险联系起来。能够在人类和动物模型中直观地辨别和定义色素表型，已经阐明了许多参与色素沉着和黑色素生物合成的基因。最近，额外的遗传流行病学研究确定了这些色素沉着基因中的一部分与黑色素瘤和其他皮肤恶性肿瘤以及光敏性风险相关。全基因组关联研究（GWAS）揭示了 MC1R、TPCN2、ASIP、KITLG、NCKX5、TYR、IRF4、OCA2 和 TYRP1 色素沉着基因中的单核苷酸多态性（SNP）或遗传变异。这些发现强调了色素沉着途径通过基因-环境相互作用对黑色素瘤易感性和肿瘤发生的贡献。由于黑色素合成途径中的色素沉着基因也会增加皮肤恶性肿瘤的风险，因此更好地了解这种关系中涉及的操作分子机制，有可能会影响未来对皮肤恶性黑色素瘤的个体风险评估。本文概述了我们目前对与黑色素瘤风险相关的色素沉着基因修饰的理解，以及这些基因如何丰富恶性黑色素瘤的临床管理、预防和早期检测。
