Germline variants of the melanocortin‐1‐receptor (MC1R) gene are the most common genetic trait predisposing to cutaneous melanoma (CM). Here, we performed a literature review and meta‐analysis of the association between MC1R gene variants and the frequency of somatic mutations of the BRAF, NRAS, and TERT genes in CM patients. We included studies published until January 2020 in MEDLINE, EMBASE, Ovid Medline, and two grey literature databases. Random effect models were used to pool study‐specific estimates into summary odds ratio (SOR) and 95% confidence intervals (CIs). Subgroup and sensitivity analyses were conducted to identify potential sources of heterogeneity and assess the robustness of pooled estimates. Twelve studies published between 2006 and 2018 (encompassing 3566 CM, mostly on nonacral sites) were included. MC1R gene variants were not significantly associated with the frequency of somatic mutations of the BRAF and NRAS genes. Only three studies focused on somatic mutations of the TERT gene promoter, all of which reported moderate‐to‐strong positive associations with MC1R germline variants. MC1R gene variants appear to make only moderate changes, if any, to the risk of BRAF‐ or NRAS‐mutant CM. The association with TERT promoter mutations is suggestive, yet it warrants confirmation as it is based on a still limited number of studies

中文翻译：

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黑色素瘤中种系 MC1R 变异和体细胞 BRAF、NRAS 和 TERT 突变的频率：文献综述和荟萃分析


黑皮质素-1-受体 ( MC1R ) 基因的种系变异是最常见的易患皮肤黑色素瘤 (CM) 的遗传特征。在此，我们对 CM 患者中MC1R基因变异与BRAF、NRAS和TERT基因体细胞突变频率之间的关联进行了文献综述和荟萃分析。我们纳入了截至 2020 年 1 月在 MEDLINE、EMBASE、Ovid Medline 和两个灰色文献数据库中发表的研究。使用随机效应模型将研究特定的估计值合并为汇总比值比 (SOR) 和 95% 置信区间 (CI)。进行亚组和敏感性分析，以确定异质性的潜在来源并评估汇总估计值的稳健性。其中包括 2006 年至 2018 年间发表的 12 项研究（包括 3566 CM，大部分在非肢端部位）。 MC1R基因变异与BRAF和NRAS基因体细胞突变频率没有显着相关。只有三项研究关注TERT基因启动子的体细胞突变，所有这些研究都报告与MC1R种系变异存在中度至强的正相关。 MC1R基因变异似乎仅对BRAF或NRAS突变 CM 的风险产生中等程度的改变（如果有的话）。与TERT启动子突变的关联具有启发性，但仍需要确认，因为它基于数量仍然有限的研究