Research Unit, Hospital Universitario Virgen de la Arrixaca, Spain.
Melanoma Res. 2010 Aug;20(4):342-8. doi: 10.1097/CMR.0b013e32833b159d.
We explored the presence of germline alterations in CDK4 exon 2, CDKN2A and MC1R in a hospital-based study of 89 melanoma cases from 89 families with at least two members affected by cutaneous melanoma. A total of 30% of the melanoma kindreds studied were carriers of CDKN2A variants, and three of these variants were known predominant alleles that have been identified earlier in Mediterranean populations (p.G101W, p.V59G and c.358delG). We observed a higher frequency of nonsynonymous MC1R variants in these Spanish melanoma kindreds (72%) with respect to the general population (60%). We observed a higher frequency of nonsynonymous MC1R variants in this Spanish melanoma kindred (72%) respect to general population (60%). A new classification of MC1R variants based on their functional effects over melanocortin-1 receptor, including the dominant-negative effect of some of them in heterozygotes, suggested an association of loss of function MC1R variants and multiple primary melanoma cases from melanoma kindred (odds ratio: 6.07, 95% confidence interval: 1.35-27.20). This study proposes the relevance of loss of function MC1R variants in the risk of melanoma in multiple primary melanoma cases with family history from areas with low melanoma incidence rate.
我们在一个基于医院的研究中，对 89 个来自 89 个有至少两名皮肤黑色素瘤患者的家族的黑色素瘤病例进行了 CDK4 外显子 2、CDKN2A 和 MC1R 种系改变的研究。所研究的黑色素瘤家族中，有 30%的家族携带有 CDKN2A 变异体，其中三种变异体是之前在地中海人群中发现的主要等位基因（p.G101W、p.V59G 和 c.358delG）。与普通人群（60%）相比，这些西班牙黑色素瘤家族中非同义 MC1R 变异体的频率更高（72%）。与普通人群（60%）相比，这些西班牙黑色素瘤家族中非同义 MC1R 变异体的频率更高（72%）。基于对黑素皮质素 1 受体的功能影响对 MC1R 变异体进行了新的分类，包括其中一些在杂合子中的显性负效应，提示功能丧失 MC1R 变异体与黑色素瘤家族中的多发性原发性黑色素瘤病例之间存在关联（比值比：6.07，95%置信区间：1.35-27.20）。本研究提出了在黑色素瘤发病率较低的地区，具有家族史的多发性原发性黑色素瘤病例中，功能丧失 MC1R 变异体与黑色素瘤风险的相关性。
