Heterogeneity in genetic susceptibility to prostate cancer.
Heterogeneity in genetic susceptibility to prostate cancer.
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DOI：
10.1016/s0953-6205(00)00136-9
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发表时间：
2001-02-01
影响因子：
8
通讯作者：
Valeri, A
中科院分区：
文献类型：
--
作者：
Cussenot, O;Valeri, A
前列腺癌的发病与衰老有关。过去10年中该病的增长情况因国家和种族群体而异，其中非裔美国男性的发病率最高，亚洲男性的发病率最低。迄今为止，只有两个明确的前列腺癌危险因素：家族聚集和种族起源。尚未发现前列腺癌的饮食或环境原因。然而，内源性因素的一些变化，例如性类固醇或 IGF1 循环水平，可能部分解释了不同人群之间观察到的风险差异。编码 5α 还原酶、雄激素受体或维生素 D 受体的基因的遗传多态性与不同程度的前列腺癌风险相关，并且可以解释不同种族群体或地理区域内风险的差异。不同的研究支持这样的理论：家族性前列腺癌可能是遗传性的，而不是由相似的生活方式造成的。因此，在建议高危家庭进行筛查时，家族遗传是必须考虑的一个参数。事实上，当前列腺癌患者的一级亲属有 1、2 和 3 名一级亲属受到影响时，其相对风险分别可达 2、5 和 11。一些家族形式似乎与一种罕见的、推定的常染色体显性基因（等位基因频率为 0.003-0.06）的传播有关，外显率很高（85 岁时为 88%）。利用这种传播模型和连锁分析，描述了1号染色体上的三个易感基因座：HPC-1（遗传性前列腺癌1：1q24-25）、PCaP（易患前列腺癌：1q42-43）和CAPB（易患前列腺和脑肿瘤：1p36）以及20号染色体上的一个基因座（HPC20：20q13）。此外，X连锁传播已被认为与另一个易感基因位点：HPCX (Xq27-28)有关。很大一部分家族性前列腺癌可能不是由于根据单基因遗传传播的一些主要基因突变的分离，而是由于在许多基因座上共享等位基因，每个基因座都会导致癌症风险的小幅增加。
The incidence of prostate cancer is related to aging. Its increase in the last 10 years, varies from country to country and according to ethnic group, with its greatest incidence among African-American males and the least among Asian males. Only two risk factors have thus far been clearly established for prostate cancer: familial aggregation and ethnic origin. No dietary or environmental cause has yet been identified for prostate cancer. However, some variations in endogenous factors, such as sex steroids or IGF1 circulating levels, may partly explain differences in risk observed between different populations. Genetic polymorphisms of genes encoding for 5alpha-reductase, androgen receptor, or vitamin D receptor have been associated with different degrees of risk for prostate cancer and may explain variations in risk among ethnic groups or within geographic areas. Different studies support the theory that familial prostate cancer may be hereditary and not due to a similar lifestyle. Thus, familial inheritance is a parameter that must be considered when advising screening in high-risk families. Indeed, the relative risk for first-degree relatives of prostate cancer patients can reach 2, 5 and 11 when, respectively, 1, 2 and 3 first-degree relatives are affected. Some familial forms appear to be associated with transmission of a rare, putative, autosomal dominant gene (0.003-0.06 allele frequency) with a high penetrance (88% at age 85). Using this transmission model and linkage analysis, three predisposing loci on chromosome 1: HPC-1 (hereditary prostate cancer 1: 1q24-25), PCaP (predisposing for prostate cancer: 1q42-43) and CAPB (predisposing for prostate and brain tumor: 1p36) and one locus on chromosome 20 (HPC20: 20q13) have been described. Moreover, X-linked transmission has been suggested and related to another predisposing gene locus: HPCX (Xq27-28). It is possible that a large proportion of familial prostate cancer is due not to segregation of a few major gene mutations transmitted according to a monogenic inheritance, but rather to familial sharing of alleles at many loci, each contributing to a small increase in cancer risk.