Easton D F, Ford D, Bishop D T
Section of Epidemiology, Institute of Cancer Research, Belmont, Surrey, England.
Am J Hum Genet. 1995 Jan;56(1):265-71.
Dominant predisposition to early-onset breast cancer and/or ovarian cancer in many families is known to be the result of germ-line mutations in a gene on chromosome 17q, known as BRCA1. In this paper we use data from families with evidence of linkage to BRCA1 to estimate the age-specific risks of breast and ovarian cancer in BRCA1-mutation carriers and to examine the variation in risk between and within families. Under the assumption of no heterogeneity of risk between families, BRCA1 is estimated to confer a breast cancer risk of 54% by age 60 years (95% confidence interval [CI] 27%-71%) and an ovarian cancer risk of 30% by age 60 years (95% CI 8%-47%). Similar lifetime-risk estimates are obtained by examining the risks of contralateral breast cancer and of ovarian cancer, in breast cancer cases in linked families. However, there is significant evidence of heterogeneity of risk between families; a much better fit to the data is obtained by assuming two BRCA1 alleles, one conferring a breast cancer risk of 62% and an ovarian cancer risk of 11% by age 60 years, the other conferring a breast cancer risk of 39% and an ovarian cancer risk of 42%, with the first allele representing 71% of all mutations (95% CI 55%-87%). There is no evidence of clustering of breast and ovarian cancer cases within families.
许多家族中早发性乳腺癌和/或卵巢癌的主要易感性已知是由17号染色体上一个名为BRCA1的基因的种系突变所致。在本文中，我们使用来自与BRCA1有连锁证据的家族的数据，来估计BRCA1突变携带者患乳腺癌和卵巢癌的年龄特异性风险，并研究家族之间和家族内部风险的差异。在假设家族之间风险无异质性的情况下，估计BRCA1在60岁时赋予乳腺癌的风险为54%（95%置信区间[CI] 27%-71%），在60岁时赋予卵巢癌的风险为30%（95% CI 8%-47%）。通过检查连锁家族中乳腺癌病例的对侧乳腺癌风险和卵巢癌风险，可获得类似的终生风险估计值。然而，有显著证据表明家族之间存在风险异质性；假设两个BRCA1等位基因，一个在60岁时赋予乳腺癌风险62%和卵巢癌风险为11%，另一个赋予乳腺癌风险39%和卵巢癌风险42%，其中第一个等位基因占所有突变的71%（95% CI 55%-87%），这样能更好地拟合数据。没有证据表明家族内部乳腺癌和卵巢癌病例存在聚集现象。
