Lerner Lane, Winn Robert, Hulbert Alicia
1University of Illinois at Chicago Cancer Center, 2Department of Surgery/Cancer Center University of Illinois at Chicago Cancer Center, University of Illinois Hospital and Health Sciences System, Chicago, USA.
J Thorac Dis. 2018 Apr;10(4):2498-2507. doi: 10.21037/jtd.2018.04.07.
Lung cancer is the most prominent cause of cancer-related mortality. Significant disparities in incidence and outcome characterize the disease's manifestations among ethnically and racially diverse populations. Complete surgical resection is the most effective curative treatment. However, success relies on early tumor detection. The National Lung Cancer Screening trial showed that lung cancer related mortality can be reduced by the use of low-dose CT (LDCT) screening. However, this test is plagued by a high false positive rate of 97% and the device itself is limited to designated cancer centers due to its expense and size. This restriction makes it difficult for underserved groups to access LDCT screening, the current standard of care. Highly sensitive and specific epigenetic DNA methylation-based biomarkers have the potential to work independently or in conjunction with LDCT screening to identify early-stage tumors. These tests could reduce unnecessary invasive confirmatory diagnostic tests and their associated morbidity and mortality. These tests also have the opportunity to bring lung cancer screening to the community thereby reducing unequal accessibility. However, epigenetic alterations are closely linked to the interplay between hereditary and environmental factors such as diet, lifestyle, ethnic ancestry, toxin exposure, residential segregation, and disparate community support structures. Despite this, the overwhelming number of early detection DNA methylation biomarker studies to date have either failed to control for ethnicity or have employed heavily Caucasian-biased patient cohorts. This review seeks to summarize the literature related to the early detection of lung cancer through molecular biomarkers among different ethnicities. Ethnical specific epigenetic biomarkers have the potential to be the first step towards an accessible, available personalized medicine approach to cancer through liquid biopsy.
肺癌是癌症相关死亡的最主要原因。在不同种族和民族人群中,该疾病的发病率和预后存在显著差异。完整的手术切除是最有效的治愈性治疗方法。然而,成功与否取决于早期肿瘤检测。国家肺癌筛查试验表明,使用低剂量CT(LDCT)筛查可降低肺癌相关死亡率。然而,这项检查存在高达97%的高假阳性率问题,并且由于其成本和尺寸,该设备本身仅限于指定的癌症中心使用。这种限制使得服务不足的群体难以获得当前的标准治疗——LDCT筛查。基于表观遗传DNA甲基化的高灵敏度和特异性生物标志物有可能独立发挥作用,或与LDCT筛查结合使用以识别早期肿瘤。这些检测可以减少不必要的侵入性确诊诊断检测及其相关的发病率和死亡率。这些检测还有机会将肺癌筛查推广到社区,从而减少可及性的不平等。然而,表观遗传改变与遗传和环境因素之间的相互作用密切相关,如饮食、生活方式、种族血统、毒素暴露、居住隔离和不同的社区支持结构。尽管如此,迄今为止,绝大多数早期检测DNA甲基化生物标志物的研究要么未能控制种族因素,要么采用了严重偏向白种人的患者队列。本综述旨在总结不同种族中通过分子生物标志物早期检测肺癌的相关文献。特定种族的表观遗传生物标志物有可能成为通过液体活检实现可及、可用的个性化癌症医学方法的第一步。