Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer.
Prevalence and contribution of BRCA1 mutations in breast cancer and ovarian cancer: results from three U.S. population-based case-control studies of ovarian cancer.
复制标题
DOI：
--
复制
发表时间：
1997-03
影响因子：
9.8
通讯作者：
A. Whittemore;G. Gong;Jacqueline;Itnyre
中科院分区：
文献类型：
--
作者：
A. Whittemore;G. Gong;Jacqueline;Itnyre
我们调查了乳腺癌和卵巢癌的家族性风险，使用的数据来自美国进行的三项基于人群的卵巢癌病例对照研究。我们对BRCA1(可能还有其他基因)突变频率的估计是基于922名卵巢癌患者(病例)和922名没有卵巢癌病史的女性(对照组)的母亲和姐妹中报告的乳腺癌和卵巢癌的发生情况。基因模型的分离分析和拟合度检验表明，罕见突变(频率为0.0014；95%可信区间为0002-011)可解释在这些家庭中观察到的乳腺癌和卵巢癌的所有聚集。到80岁时，突变携带者患乳腺癌的风险估计为73.5%，非携带者为6.8%。卵巢癌的相应估计在携带者中为27.8%，在非携带者中为1.8%。对于携带者的癌症风险，这些估计低于从癌症高发家庭获得的估计。据估计，到80岁时，美国所有癌症诊断中因生殖系BRCA1突变而确诊的比例分别为3.0%和4.4%。在169名交界性卵巢癌患者的家族中，乳腺癌和卵巢癌的聚集性不如浸润性癌症患者的家族中明显。尽管非白人和西班牙裔病例(N=99)的数量很少，但先证者的种族没有不同的家庭聚集性。
We investigate the familial risks of cancers of the breast and ovary, using data pooled from three population-based case-control studies of ovarian cancer that were conducted in the United States. We base estimates of the frequency of mutations of BRCA1 (and possibly other genes) on the reported occurrence of breast cancer and ovarian cancer in the mothers and sisters of 922 women with incident ovarian cancer (cases) and in 922 women with no history of ovarian cancer (controls). Segregation analysis and goodness-of-fit testing of genetic models suggest that rare mutations (frequency .0014; 95% confidence interval .0002-.011) account for all the observed aggregation of breast cancer and ovarian cancer in these families. The estimated risk of breast cancer by age 80 years is 73.5% in mutation carriers and 6.8% in noncarriers. The corresponding estimates for ovarian cancer are 27.8% in carriers and 1.8% in noncarriers. For cancer risk in carriers, these estimates are lower than those obtained from families selected for high cancer prevalence. The estimated proportion of all U.S. cancer diagnoses, by age 80 years, that are due to germ-line BRCA1 mutations is 3.0% for breast cancer and 4.4% for ovarian cancer. Aggregation of breast cancer and ovarian cancer was less evident in the families of 169 cases with borderline ovarian cancers than in the families of cases with invasive cancers. Familial aggregation did not differ by the ethnicity of the probands, although the number of non-White and Hispanic cases (N = 99) was sparse.