黑皮质素-1受体(MC1R)基因的种系变体是皮肤黑色素瘤(CM)最常见的遗传性状。这里,我们对MC1R基因变异与BRAF体细胞突变频率之间的相关性进行了文献综述和荟萃分析,NRAS,CM患者的TERT基因。我们纳入了直到2020年1月在MEDLINE上发表的研究,EMBASE,OvidMedline,和两个灰色文献数据库。使用随机效应模型将特定研究的估计值汇总为汇总比值比(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,并评估合并估计的稳健性。2006年至2018年发表的12项研究(涵盖3566厘米,主要在非accal部位)被包括在内。MC1R基因变异与BRAF和NRAS基因的体细胞突变频率没有显着相关。只有三项研究集中在TERT基因启动子的体细胞突变上,所有这些研究都报告了与MC1R种系变异体的中度到强正相关.MC1R基因变异似乎只产生适度的变化,如果有的话,BRAF或NRAS突变CM的风险。与TERT启动子突变的关联提示,然而,它值得确认,因为它是基于仍然有限数量的研究。
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.