Department of Dermatology, Stanford University School of Medicine, Stanford, California.
Quantitative Sciences Unit, Stanford University School of Medicine, Stanford, California.
J Am Acad Dermatol. 2018 Jul;79(1):36-41.e10. doi: 10.1016/j.jaad.2018.02.052. Epub 2018 Mar 1.
Single-nucleotide polymorphisms (SNPs) associated with melanoma have been identified though genome-wide association studies. However, the combined impact of these SNPs on melanoma development remains unclear, particularly in postmenopausal women who carry a lower melanoma risk.
We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women.
Genetic risk scores were calculated using 21 genome-wide association study-significant SNPs. Their combined effect on melanoma development was evaluated in 19,102 postmenopausal white women in the clinical trial and observational study arms of the Women's Health Initiative dataset.
Compared to the tertile of weighted genetic risk score with the lowest genetic risk, the women in the tertile with the highest genetic risk were 1.9 times more likely to develop melanoma (95% confidence interval 1.50-2.42). The incremental change in c-index from adding genetic risk scores to age were 0.075 (95% confidence interval 0.041-0.109) for incident melanoma.
Limitations include a lack of information on nevi count, Fitzpatrick skin type, family history of melanoma, and potential reporting and selection bias in the Women's Health Initiative cohort.
Higher genetic risk is associated with increased melanoma prevalence and incidence in postmenopausal women, but current genetic information may have a limited role in risk prediction when phenotypic information is available.
通过全基因组关联研究已经确定了与黑色素瘤相关的单核苷酸多态性（SNPs）。然而，这些 SNPs 对黑色素瘤发展的综合影响仍不清楚，尤其是在携带较低黑色素瘤风险的绝经后妇女中。
我们研究了多基因风险评分对绝经后妇女黑色素瘤发展的贡献。
使用 21 个全基因组关联研究显著 SNPs 计算遗传风险评分。在妇女健康倡议数据集的临床试验和观察研究臂中，评估了这些 SNPs 对 19102 名绝经后白人妇女黑色素瘤发展的综合影响。
与遗传风险最低的 tertile 相比，遗传风险最高的 tertile 中女性患黑色素瘤的风险高 1.9 倍（95%置信区间 1.50-2.42）。从加性遗传风险评分到年龄的 c 指数增量为 0.075（95%置信区间 0.041-0.109），用于预测黑色素瘤的发生。
局限性包括缺乏痣计数、Fitzpatrick 皮肤类型、黑色素瘤家族史以及妇女健康倡议队列中的潜在报告和选择偏倚。
更高的遗传风险与绝经后妇女黑色素瘤的患病率和发病率增加相关，但在有表型信息时，当前的遗传信息在风险预测中的作用可能有限。
