Cornelisse C J, Devilee P
Department of Pathology, Leiden University Medical Centre, The Netherlands.
Patient Educ Couns. 1997 Sep-Oct;32(1-2):9-17. doi: 10.1016/s0738-3991(97)00059-1.
During the past decade molecular biology and molecular genetics have greatly increased our understanding of the basic mechanisms in cancer development. The essential outcome of these molecular studies is that cancer can be considered as a genetic disease of cells. Both the non-hereditary (sporadic) cancers, as well as the hereditary forms of cancer are caused by genetic accidents that perturb the complex and delicate cellular growth control systems. Thus, at the molecular level, no principal difference exists between hereditary- and non-hereditary forms of cancer and it can be stated that both at the level of the single cell as well at the level of the individual, cancer is a genetic disease. Whereas in hereditary cancer, the risk gene is passed through the germline to the next generation, in sporadic cancer, a cancer cells passes its abnormal genes to its daughter cells at cell division. It is therefore not surprising that one of the main priorities in cancer research today is the identification of the culprit genes and characterizing the function of their normal products. Genes associated with hereditary cancer syndromes essentially encompass two classes of genes viz. tumor suppressor genes and genes controlling genomic stability (DNA-mismatch repair genes). Although germline mutations in these susceptibility genes are associated with significantly increased cancer risk, even up to 90%, additional genetic factors and interaction with environmental factors eventually determine if a carrier of a germline mutation will develop cancer.
在过去十年中,分子生物学和分子遗传学极大地增进了我们对癌症发生基本机制的理解。这些分子研究的基本成果是,癌症可被视为一种细胞的遗传性疾病。无论是非遗传性(散发性)癌症,还是遗传性癌症,都是由扰乱复杂而精细的细胞生长控制系统的遗传意外所导致的。因此,在分子层面,遗传性和非遗传性癌症形式之间不存在本质区别,可以说,无论是在单细胞水平还是个体水平,癌症都是一种遗传性疾病。在遗传性癌症中,风险基因通过种系传递给下一代,而在散发性癌症中,癌细胞在细胞分裂时将其异常基因传递给子细胞。因此,当今癌症研究的主要优先事项之一是识别罪魁祸首基因并表征其正常产物的功能,这并不奇怪。与遗传性癌症综合征相关的基因主要包括两类基因,即肿瘤抑制基因和控制基因组稳定性的基因(DNA错配修复基因)。尽管这些易感基因中的种系突变与显著增加的癌症风险相关,甚至高达90%,但额外的遗传因素以及与环境因素的相互作用最终决定了种系突变携带者是否会患癌症。