Einspahr J G, Alberts D S, Gapstur S M, Bostick R M, Emerson S S, Gerner E W
University of Arizona Cancer Biology Graduate Program, Arizona Cancer Center, Tucson 85724, USA.
Cancer Epidemiol Biomarkers Prev. 1997 Jan;6(1):37-48.
Surrogate end-point biomarkers (SEBs) have become widely used in short-term cancer chemoprevention trials in place of cancer end points. This paper discusses criteria relevant to the selection and validation of SEBs for colon cancer risk and the use of SEBs in colon cancer chemoprevention trials. As with a number of other cancers, colon carcinogenesis is the result of a multistep process in which an increasing number of alterations, including specific gene mutations, occur as cells progress from normal to precancerous states of increasing size and dysplasia to cancer and finally to metastatic disease. Ideally, a SEB would show differential expression between the various phases of colon carcinogenesis (i.e., normal, premalignant, and malignant tissues) and be associated with risk of colon cancer. Some SEBs that do not meet these criteria may still be useful for demonstrating the effect of a particular agent. It is also necessary that a SEB be measured in tissues (or other sample material) accessible for multiple and sequential sampling and allow for development of appropriate quality control procedures. Some SEBs must have the potential for modulation by chemopreventive agents. Validation of SEBs for use in chemoprevention studies requires that a relationship between the marker and subsequent risk of cancer be established. Also, the assay reliability and accuracy for each SEB must be determined adequately in well-designed prospective studies.
替代终点生物标志物（SEBs）已广泛应用于短期癌症化学预防试验，以替代癌症终点。本文讨论了与结肠癌风险SEBs的选择和验证相关的标准，以及SEBs在结肠癌化学预防试验中的应用。与许多其他癌症一样，结肠癌的发生是一个多步骤过程的结果，在此过程中，随着细胞从正常状态发展到大小和发育异常不断增加的癌前状态，再到癌症，最终发展为转移性疾病，会出现越来越多的改变，包括特定基因突变。理想情况下，一个SEB应在结肠癌发生的各个阶段（即正常、癌前和恶性组织）表现出差异表达，并与结肠癌风险相关。一些不符合这些标准的SEB可能仍有助于证明特定药物的效果。此外，SEB必须能够在可进行多次和连续采样的组织（或其他样本材料）中进行测量，并允许制定适当的质量控制程序。一些SEB必须具有被化学预防剂调节的潜力。用于化学预防研究的SEB的验证要求建立标志物与随后癌症风险之间的关系。此外，必须在设计良好的前瞻性研究中充分确定每个SEB的检测可靠性和准确性。
