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结直肠癌:从预防到个性化医疗

Colorectal cancer: from prevention to personalized medicine.

作者信息

Binefa Gemma, Rodríguez-Moranta Francisco, Teule Alex, Medina-Hayas Manuel

机构信息

Gemma Binefa, Cancer Prevention and Control Program, Catalan Institute of Oncology, IDIBELL, CIBERESP, Hospitalet de Llobregat, 08908 Barcelona, Spain.

出版信息

World J Gastroenterol. 2014 Jun 14;20(22):6786-808. doi: 10.3748/wjg.v20.i22.6786.

Abstract

Colorectal cancer (CRC) is a very heterogeneous disease that is caused by the interaction of genetic and environmental factors. CRC develops through a gradual accumulation of genetic and epigenetic changes, leading to the transformation of normal colonic mucosa into invasive cancer. CRC is one of the most prevalent and incident cancers worldwide, as well as one of the most deadly. Approximately 1235108 people are diagnosed annually with CRC, and 609051 die from CRC annually. The World Health Organization estimates an increase of 77% in the number of newly diagnosed cases of CRC and an increase of 80% in deaths from CRC by 2030. The incidence of CRC can benefit from different strategies depending on its stage: health promotion through health education campaigns (when the disease is not yet present), the implementation of screening programs (for detection of the disease in its early stages), and the development of nearly personalized treatments according to both patient characteristics (age, sex) and the cancer itself (gene expression). Although there are different strategies for screening and although the number of such strategies is increasing due to the potential of emerging technologies in molecular marker application, not all strategies meet the criteria required for screening tests in population programs; the three most accepted tests are the fecal occult blood test (FOBT), colonoscopy and sigmoidoscopy. FOBT is the most used method for CRC screening worldwide and is also the primary choice in most population-based screening programs in Europe. Due to its non-invasive nature and low cost, it is one of the most accepted techniques by population. CRC is a very heterogeneous disease, and with a few exceptions (APC, p53, KRAS), most of the genes involved in CRC are observed in a small percentage of cases. The design of genetic and epigenetic marker panels that are able to provide maximum coverage in the diagnosis of colorectal neoplasia seems a reasonable strategy. In recent years, the use of DNA, RNA and protein markers in different biological samples has been explored as strategies for CRC diagnosis. Although there is not yet sufficient evidence to recommend the analysis of biomarkers such as DNA, RNA or proteins in the blood or stool, it is likely that given the quick progression of technology tools in molecular biology, increasingly sensitive and less expensive, these tools will gradually be employed in clinical practice and will likely be developed in mass.

摘要

结直肠癌(CRC)是一种非常异质性的疾病,由遗传和环境因素相互作用引起。CRC通过遗传和表观遗传变化的逐渐积累而发展,导致正常结肠黏膜转变为浸润性癌。CRC是全球最常见和发病率最高的癌症之一,也是最致命的癌症之一。每年约有1235108人被诊断为CRC,每年有609051人死于CRC。世界卫生组织估计,到2030年,新诊断的CRC病例数将增加77%,CRC死亡人数将增加80%。CRC的发病率可根据其阶段从不同策略中受益:通过健康教育活动进行健康促进(当疾病尚未出现时)、实施筛查计划(用于在疾病早期检测)以及根据患者特征(年龄、性别)和癌症本身(基因表达)制定近乎个性化的治疗方案。尽管有不同的筛查策略,并且由于新兴技术在分子标志物应用方面的潜力,此类策略的数量正在增加,但并非所有策略都符合人群计划中筛查测试所需的标准;最被认可的三种测试是粪便潜血试验(FOBT)、结肠镜检查和乙状结肠镜检查。FOBT是全球CRC筛查中使用最广泛的方法,也是欧洲大多数基于人群的筛查计划的首选。由于其非侵入性和低成本,它是人群最认可的技术之一。CRC是一种非常异质性的疾病,除了少数例外(APC、p53、KRAS),大多数与CRC相关的基因在少数病例中被观察到。设计能够在结直肠肿瘤诊断中提供最大覆盖范围的遗传和表观遗传标志物面板似乎是一种合理的策略。近年来,已经探索了在不同生物样本中使用DNA、RNA和蛋白质标志物作为CRC诊断的策略。尽管尚无足够证据推荐分析血液或粪便中的DNA、RNA或蛋白质等生物标志物,但鉴于分子生物学技术工具的快速发展,越来越灵敏且成本更低,这些工具将逐渐应用于临床实践,并可能大规模开发。

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