Becher H, Chang-Claude J
Division of Epidemiology, German Cancer Research Center, Heidelberg, Germany.
Genet Epidemiol. 1996;13(3):229-42. doi: 10.1002/(SICI)1098-2272(1996)13:3<229::AID-GEPI1>3.0.CO;2-1.
For many chronic diseases, including most of the common cancers, a family history is known to be a strong independent risk factor. For breast cancer, estimation of risk as a function of family history is considered to provide useful risk assessment for women with a family history of breast cancer. Detailed tables that predict the cumulative risk of breast cancer at specific ages based on various combinations of family history have been constructed for the American white population. Most chronic diseases, however, have a multiple etiology, with multiple genetic and environmental factors. Family history can thus be a result of different susceptibility loci and the aggregation of sporadic cases by chance. Since the relative contribution of the genetic factor may differ in different populations, these tables may not be directly applicable to other populations. We present a method to decompose available estimates of risk based on family history for an arbitrary disease into probabilities for genotype frequency given a particular family history and for disease probabilities by genotype carrier status. These can be reconstructed to obtain risk estimates for different populations. Implicit assumptions are made in the estimation process. These are based on the current state of knowledge and can be updated as further knowledge accumulates.
对于许多慢性疾病，包括大多数常见癌症，家族病史是一个强有力的独立风险因素。对于乳腺癌而言，根据家族病史估算风险被认为可为有乳腺癌家族史的女性提供有用的风险评估。针对美国白人人群，已构建了详细表格，可根据家族病史的各种组合预测特定年龄患乳腺癌的累积风险。然而，大多数慢性疾病具有多种病因，涉及多个遗传和环境因素。家族病史因此可能是不同易感基因座以及偶发性病例偶然聚集的结果。由于遗传因素的相对贡献在不同人群中可能有所不同，这些表格可能无法直接应用于其他人群。我们提出一种方法，可将基于家族病史的任意疾病的可用风险估计分解为给定特定家族病史时的基因型频率概率以及按基因型携带者状态的疾病概率。通过这些概率可以重新构建以获得不同人群的风险估计。在估计过程中做出了一些隐含假设。这些假设基于当前的知识状态，并且可以随着更多知识的积累而更新。
