Department of Internal Medicine and Medical Specialties, University of Genoa, Genoa, Italy.
Exp Dermatol. 2012 Sep;21(9):718-20. doi: 10.1111/j.1600-0625.2012.01549.x.
Host, environmental and genetic factors differently modulate cutaneous melanoma (CM) risk across populations. Currently, the main genetic risk determinants are germline mutations in the major known high-risk susceptibility genes, CDKN2A and CDK4, and variants of the low-risk gene MC1R, which is key in the pigmentation process. This case-control study aimed at investigating the influence of the main host and environmental risk factors and of MC1R variation on CM risk in 390 CDKN2A-negative and 49 CDKN2A-positive Italian individuals. Multivariate analysis showed that MC1R variation, number of nevi and childhood sunburns doubled CM risk in CDKN2A-negative individuals. In CDKN2A-positive individuals, family history of CM and presence of atypical nevi, rather than MC1R status, modified risk (20.75- and 2.83-fold, respectively). Occupational sun exposure increased CM risk (three to sixfold) in both CDKN2A-negative and CDKN2A-positive individuals, reflecting the occupational habits of the Ligurian population and the geographical position of Liguria.
宿主、环境和遗传因素在不同人群中对皮肤黑色素瘤（CM）的风险有不同的影响。目前，主要的遗传风险决定因素是已知高风险易感基因 CDKN2A 和 CDK4 中的种系突变，以及低风险基因 MC1R 的变体，MC1R 是色素沉着过程中的关键基因。本病例对照研究旨在调查主要宿主和环境风险因素以及 MC1R 变异对 390 名 CDKN2A 阴性和 49 名 CDKN2A 阳性意大利个体 CM 风险的影响。多变量分析表明，MC1R 变异、痣的数量和儿童期晒伤使 CDKN2A 阴性个体的 CM 风险增加了一倍。在 CDKN2A 阳性个体中，CM 的家族史和不典型痣的存在（而非 MC1R 状态）改变了风险（分别增加了 20.75 倍和 2.83 倍）。职业性阳光暴露增加了 CDKN2A 阴性和 CDKN2A 阳性个体的 CM 风险（增加了 3 至 6 倍），这反映了利古里亚地区人群的职业习惯和利古里亚地区的地理位置。
