Newman B, Austin M A, Lee M, King M C
School of Public Health, University of California, Berkeley 94720.
Proc Natl Acad Sci U S A. 1988 May;85(9):3044-8. doi: 10.1073/pnas.85.9.3044.
Segregation analysis of breast cancer in families can provide the logical basis and the specific genetic models for mapping and identifying genes responsible for human breast cancer. Patterns of breast cancer occurrence in families were investigated by complex segregation analysis. In a sample of 1579 nuclear families ascertained through a population-based series of probands, an autosomal dominant model with a highly penetrant susceptibility allele fully explained disease clustering. From the maximum-likelihood Mendelian model, the frequency of the susceptibility allele was 0.0006 in the general population, and lifetime risk of breast cancer was 0.82 among susceptible women and 0.08 among women without the susceptibility allele. Inherited susceptibility affected only 4% of families in the sample: multiple cases of this relatively common disease occurred in other families by chance. The same genetic models, with higher gene frequency, explained disease clustering in an extended kindred at high risk of breast cancer. Evidence for a highly penetrant, autosomal dominant susceptibility allele for breast cancer in a high-risk family and the general population suggests that high-risk families can serve as models for understanding breast cancer in the population as a whole.
对家族性乳腺癌进行分离分析可为绘制和鉴定导致人类乳腺癌的基因提供逻辑依据和特定的遗传模型。通过复杂分离分析研究了家族中乳腺癌的发病模式。在通过一系列基于人群的先证者确定的1579个核心家庭样本中，具有高外显率易感等位基因的常染色体显性模型充分解释了疾病的聚集现象。根据最大似然孟德尔模型，在一般人群中，易感等位基因的频率为0.0006，易感女性患乳腺癌的终生风险为0.82，而没有易感等位基因的女性患乳腺癌的终生风险为0.08。遗传易感性仅影响样本中4%的家庭：这种相对常见疾病的多例在其他家庭中是偶然发生的。相同的遗传模型，基因频率更高，解释了一个患乳腺癌高风险的扩展亲属中疾病的聚集现象。在一个高风险家族和一般人群中存在一个高外显率、常染色体显性乳腺癌易感等位基因的证据表明，高风险家族可作为理解整个人群中乳腺癌的模型。
