分子流行病学的原理与应用及对人前列腺癌的研究

PRINCIPLES AND APPLICATIONS OF MOLECULAR EPIDEMIOLOGY AND STUDIES OF HUMAN PROSTATIC CARCINOMA

癌瘤形成是一个涉及瘤的起始、促进、转变、演进和建成的多阶段过程。与人癌危险（ｃａｎｃｅｒｒｉｓｋ）有关的致癌因子，有的已知，有的尚不清楚，包括遗传易感性，以及职业的、环境的、和生活方式等因子。可疑致癌因子与癌危险之间的联系通常是用经典流行病学方法来研究，就是将受到暴露的一组人群与年龄性别配对与未受到暴露的对照组比较。即使用此法证实有联系，但仍得不到其中的因果关系。况且，经典流行病学技术用以估计个体的癌危险，其应用性是有限的。分子流行病学是一新兴领域，着重于用分子遗传学和生化技术来评估个体的癌危险。它能在临床症状发生前，就能用生物学标志来鉴定癌危险，行施有效的干预。从体内外实验模型，综合基因结构、功能和异常的知识，并建立一系列与分子的和遗传的损伤，以及与瘤诊断和预后测定有关的生物学标志，分子流行病学潜在地帮助人们获知人类健康和疾病的更高认识，从而可更适当地推论到更大的人群中去。本文试图用概念图式介绍关键方法，来阐明这些原理，并提供如何用特定的研究技术来探讨前列腺细胞转化和癌变的问题。

Cancer formation is a multistage process involving tumor initiation, promotion,conversion,progression,and establishment.Genetic susceptibitity factors,as well as occupational,environmental,and lifestyle/recreational exposure to a host of factors including known and yet-to-be-characterizd caercinogens contribute to cancer risks in humans.The association of a suspected carcinogenic exposure and cancer/disease risk can be and has been traditionally studied in populations using classic epidemiologic methodologies in which factors affecting the frequency of appearance of a particular cancer/disease are typically evaluated by calculating and comparing the mean relatedness of a group with that cancer/disease with the mean of a group of age/and sex/matched controls.Even though inferences made from such approaches regarding a particular type of cancer/disease allow associations to be identified,causality remains not determinable.Moreover, classic epidemiologic techniques have limited applicability insofar as the assessment of risks in individuall is concerned.Molecular epidemiology is an emerging field that attempts to circumvent some of the aforementioned difficulties associated with classical epidemiologic approaches by emphasizing the use of molecular genetics and biochemical tools to evaluate an individual's cancer risks.It aims to prevent disease by using biological markers to identify risks well before clinical onset to allow effective intervention By integrating our understanding of gene structure,function, and abnormalities,with the development of in vitro and in vivo laboratory models,and the establishment of a battery of biological markers relevant to the measurement of molecular and genetic damages as well as to the diagnosis and prognosis of neoplastic diseases,molecular epidemiology can potentially help us to achieve the goal of advancing knowledge abot health and disease among groups of people in ways that are appropriate for inference to larger populations.This report will attempt to illustrate these principles by presenting key methods in a conceptual framework to show how particular research techniques have provided insights into the probolems of prostate cell transtormation and carcinogenesis.