Background

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.

Objective

We examine the contribution of a combined polygenic risk score on melanoma development in postmenopausal women.

Methods

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.

Results

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

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.

Conclusion

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.

中文翻译：

---

妇女健康倡议队列中使用多基因座遗传风险评分的黑色素瘤风险预测

背景

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（SNP）。但是，这些SNP对黑素瘤发展的综合影响仍不清楚，尤其是在绝经后妇女中，黑素瘤风险较低。

客观的

我们检查了组合的多基因风险评分对绝经后妇女黑色素瘤发展的贡献。

方法

使用21个全基因组关联研究-显着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小组中，对19102名绝经后的白人妇女评估了它们对黑素瘤发展的综合影响。

结果

与具有最低遗传风险的加权遗传风险评分三分位数相比，具有最高遗传风险的三分位数女性罹患黑色素瘤的可能性高1.9倍（95％置信区间1.50-2.42）。对于黑色素瘤，从增加遗传风险评分到年龄，c指数的增量变化为0.075（95％置信区间0.041-0.109）。

局限性

局限性包括缺乏关于痣计数，费兹帕特里克皮肤类型，黑色素瘤家族史的信息，以及妇女健康倡议队列中潜在的报告和选择偏见。

结论

较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，但是，当可获得表型信息时，当前的遗传信息在风险预测中的作用可能有限。