Department of Gynecologic Oncology and Reproductive Medicine, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas.
Cancer. 2020 Feb 15;126(4):800-807. doi: 10.1002/cncr.32598. Epub 2019 Nov 15.
Racial disparities in cancer outcomes are increasingly recognized, but comprehensive analyses, including molecular studies, are limited. The objective of the current study was to perform a pan-cancer clinical and epigenetic molecular analysis of outcomes in African American (AA) and European American (EA) patients.
Cross-platform analyses using cancer databases (the Surveillance, Epidemiology, and End Results program database and the National Cancer Data Base) and a molecular database (The Cancer Genome Ancestry Atlas) were performed to evaluate clinical and epigenetic molecular differences between AA and EA patients based on genetic ancestry.
In the primary pan-cancer survival analysis using the Surveillance, Epidemiology, and End Results database (2,045,839 patients; 87.5% EA and 12.5% AA), AA patients had higher mortality rates for 28 of 42 cancer types analyzed (hazard ratio, >1.0). AAs continued to have higher mortality in 13 cancer types after adjustment for socioeconomic variables using the National Cancer Database (5,150,023 patients; 11.6% AA and 88.4% EA). Then, molecular features of 5,283 tumors were analyzed in patients who had genetic ancestry data available (87.2% EA and 12.8% AA). Genes were identified with altered DNA methylation along with increased microRNA expression levels unique to AA patients that are associated with cancer drug resistance. Increased miRNAs (miR-15a, miR-17, miR-130-3p, miR-181a) were noted in common among AAs with breast, kidney, thyroid, or prostate carcinomas.
The current results identified epigenetic features in AA patients who have cancer that may contribute to higher mortality rates compared with EA patients who have cancer. Therefore, a focus on molecular signatures unique to AAs may identify actionable molecular abnormalities.
癌症结局的种族差异日益受到关注,但综合分析,包括分子研究,仍很有限。本研究的目的是对非裔美国人和欧洲裔美国人患者的癌症结果进行泛癌症临床和表观遗传学分子分析。
使用癌症数据库(监测、流行病学和最终结果数据库和国家癌症数据库)和分子数据库(癌症基因组起源图谱)进行跨平台分析,根据遗传起源评估非裔美国人和欧洲裔美国人患者之间的临床和表观遗传学分子差异。
在使用监测、流行病学和最终结果数据库进行的主要泛癌症生存分析中(2045839 例患者;87.5%为欧洲裔美国人,12.5%为非裔美国人),28/42 种分析的癌症类型中,非裔美国人的死亡率更高(风险比>1.0)。在使用国家癌症数据库调整社会经济变量后,非裔美国人在 13 种癌症类型中仍然具有更高的死亡率(5150033 例患者;11.6%为非裔美国人,88.4%为欧洲裔美国人)。然后,分析了有遗传起源数据的 5283 例肿瘤的分子特征(87.2%为欧洲裔美国人,12.8%为非裔美国人)。确定了一些基因,这些基因的 DNA 甲基化发生改变,同时还存在非裔美国人特有的 miRNA 表达水平升高,这些与癌症药物耐药性有关。在非裔美国人的乳腺癌、肾癌、甲状腺癌或前列腺癌中,miR-15a、miR-17、miR-130-3p、miR-181a 等 miRNA 水平升高较为常见。
目前的研究结果确定了非裔美国癌症患者的表观遗传学特征,这些特征可能导致与癌症患者相比死亡率更高。因此,关注非裔美国人特有的分子特征可能会发现可治疗的分子异常。