Whittemore A S, Gong G, Itnyre J
Department of Health Research and Policy, Stanford University School of Medicine, CA 94305-5092, USA.
Am J Hum Genet. 1997 Mar;60(3):496-504.
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.
我们利用在美国开展的三项基于人群的卵巢癌病例对照研究汇总的数据，调查乳腺癌和卵巢癌的家族风险。我们根据922例新发卵巢癌女性（病例组）的母亲和姐妹以及922例无卵巢癌病史女性（对照组）中报告的乳腺癌和卵巢癌发生情况，对BRCA1（可能还有其他基因）突变频率进行估计。遗传模型的分离分析和拟合优度检验表明，罕见突变（频率为0.0014；95%置信区间为0.0002 - 0.011）解释了这些家族中观察到的所有乳腺癌和卵巢癌聚集现象。突变携带者到80岁时患乳腺癌的估计风险为73.5%，非携带者为6.8%。卵巢癌的相应估计值在携带者中为27.8%，在非携带者中为1.8%。对于携带者的癌症风险，这些估计值低于从高癌症患病率家庭中获得的估计值。到80岁时，估计美国所有癌症诊断中，由种系BRCA1突变导致的乳腺癌占3.0%，卵巢癌占4.4%。与浸润性癌病例的家族相比，169例交界性卵巢癌病例的家族中乳腺癌和卵巢癌的聚集现象不那么明显。尽管非白人和西班牙裔病例数量（N = 99）较少，但先证者的种族对家族聚集情况没有影响。
