背景:肝内胆管癌(iCCA)患者的发病率和预后存在种族和性别差异,然而,可能导致不同结局的基于种族和性别的iCCA潜在基因组变异尚未得到很好的研究.
方法:分析了来自美国癌症研究协会GENIE注册(15.0版)的数据,以评估iCCA的遗传变异。经组织学证实的iCCA接受下一代测序的成年患者(年龄>18岁)包括在分析队列中。检查了iCCA基因组谱中的种族和性别差异。
结果:该研究招募了来自19个中心的1068名患者(White,71.9%;黑色,5.1%;亚洲,8.4%,other,14.6%)。男女比例为1:1。大多数患者有原发性肿瘤(73.7%),而23.0%有转移性疾病测序。虽然IDH1突变在白人和黑人患者中更频繁发生(20.8%与5.6%;p=0.021),FGFR2突变在黑人与白人人群中更常见(27.8%与16.1%;p=0.08)。男性比女性更容易患TP53突变(24.3%vs.18.2%,p=0.016),而女性更频繁地患有IDH1(23.3%vs16.0%),FGFR2(21.0%vs.11.3%),和BAP1(23.4%与14.5%)突变高于男性(均p<0.05)。在不同种族和性别之间,注意到iCCA中其他常见基因组改变的患病率存在明显差异。
结论:在不同种族和性别的iCCA中存在不同的基因组变异。iCCA患者突变谱的差异突出了在iCCA临床试验中包括不同患者群体的重要性,以及识别不同遗传驱动因素的重要性,这些因素可能是治疗不同患者队列的目标。
BACKGROUND: Racial and sex disparities in the incidence and outcomes of patients with intrahepatic cholangiocarcinoma (iCCA) exist, yet potential genomic variations of iCCA based on race and sex that might be contributing to disparate outcomes have not been well studied.
METHODS: Data from the American Association for Cancer Research Project GENIE registry (version 15.0) were analyzed to assess genetic variations in iCCA. Adult patients (age >18 years) with histologically confirmed iCCA who underwent next-generation sequencing were included in the analytic cohort. Racial and sex variations in genomic profiling of iCCA were examined.
RESULTS: The study enrolled 1068 patients from 19 centers (White, 71.9%; Black, 5.1%; Asian, 8.4%, other, 14.6%). The male-to-female ratio was 1:1. The majority of the patients had primary tumors (73.7%), whereas 23.0% had metastatic disease sequenced. While IDH1 mutations occurred more frequently in White versus Black patients (20.8% vs. 5.6%; p = 0.021), FGFR2 mutations tended to be more common among Black versus White populations (27.8% vs. 16.1%; p = 0.08). Males were more likely to have TP53 mutations than females (24.3% vs. 18.2%, p = 0.016), whereas females more frequently had IDH1 (23.3% vs 16.0 %), FGFR2 (21.0% vs. 11.3%), and BAP1 (23.4% vs. 14.5%) mutations than males (all p < 0.05). Marked variations in the prevalence of other common genomic alterations in iCCA were noted across different races and sexes.
CONCLUSIONS: Distinct genomic variations exist in iCCA across race and sex. Differences in mutational profiles of iCCA patients highlight the importance of including a diverse patient population in iCCA clinical trials as well as the importance of recognizing different genetic drivers that may be targetable to treat distinct patient cohorts.