Cussenot O, Valeri A, Berthon P, Fournier G, Mangin P
Département d'Urologie, Université Paris-VII, Hôpital Saint-Louis, France.
Urol Int. 1998;60 Suppl 2:30-4; discussion 35. doi: 10.1159/000056549.
The incidence of prostate cancer (CaP) and its increase in the last 10 years vary both from country to country and according to the ethnic group, with the highest incidence reported for Afro-Americans and the lowest for Asian men. To date, only three risk factors have been established for CaP: age; familial aggregation of CaP, and ethnic origins. No dietary or environment-related cause has been established. However, some variations in endogenous genetic factors may help explain differences in risk among ethnic groups or geographic areas. Similarly, certain genetic polymorphisms of genes encoding for 5alpha-reductase, androgen receptor or vitamin D, have been associated with different levels of CaP risk, and could explain the variations observed between populations. Different studies support the view that familial CaP may truly be hereditary, and not due to a similar lifestyle. Thus, familial inheritance is a parameter that needs to be considered in recommending screening for high-risk families. Indeed, when 1, 2, and 3 first-degree relatives are affected, the relative risk of first-degree relatives of CaP patients may increase to 2, 5, and 11%, respectively. Some familial forms appear to be associated with transmission of a rare putative dominant gene with a high penetrance (88% at age 85), with the cumulative proportion of CaP attributable to this gene being more marked for younger patients (a 43 versus a 34% risk of CaP appearing before the age of 55 versus 70 years). Using this transmission model and linkage analysis, a predisposing locus on chromosome 1q24-25 (HPC-1) has been described. Moreover, recessive and X-linked transmission has been suggested, showing that a large proportion of familial CaP may not be due to segregation of a few major gene mutations, but rather to familial sharing of alleles at many loci, each contributing to a small increase in cancer risk. Candidate genes may be the same suppressor genes that are involved in other cancers and in sporadic CaP.
前列腺癌（CaP）的发病率及其在过去10年中的增长在不同国家以及不同种族之间存在差异，其中非裔美国人的发病率最高，亚洲男性的发病率最低。迄今为止，仅确定了CaP的三个风险因素：年龄、CaP的家族聚集性和种族起源。尚未确定与饮食或环境相关的病因。然而，内源性遗传因素的某些差异可能有助于解释不同种族或地理区域之间风险的差异。同样，编码5α-还原酶、雄激素受体或维生素D的基因的某些遗传多态性与不同水平的CaP风险相关，并可以解释人群之间观察到的差异。不同的研究支持这样一种观点，即家族性CaP可能确实是遗传性的，而不是由于相似的生活方式。因此，在建议对高危家庭进行筛查时，家族遗传是一个需要考虑的参数。事实上，当一级亲属中有1人、2人和3人患病时，CaP患者一级亲属的相对风险可能分别增加到2%、5%和11%。一些家族性形式似乎与一种罕见的假定显性基因的传递有关，该基因具有高外显率（85岁时为88%），对于年轻患者，归因于该基因的CaP累积比例更为明显（55岁之前出现CaP的风险为43%，而70岁时为34%）。使用这种传递模型和连锁分析，已经描述了1号染色体q24-25区域（HPC-1）上的一个易感位点。此外，有人提出了隐性和X连锁传递，这表明很大一部分家族性CaP可能不是由于少数主要基因突变的分离，而是由于许多位点上等位基因的家族共享，每个位点都导致癌症风险略有增加。候选基因可能与其他癌症和散发性CaP中涉及的相同抑制基因相同。
