The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews
The risk of cancer associated with specific mutations of BRCA1 and BRCA2 among Ashkenazi Jews
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DOI：
10.1056/nejm199705153362001
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发表时间：
1997-05-15
影响因子：
158.5
通讯作者：
Tucker, MA
中科院分区：
文献类型：
--
作者：
Struewing, JP;Hartge, P;Tucker, MA
背景：据估计，来自癌症高危家族的BRCA 1和BRCA 2生殖系突变携带者患乳腺癌的风险为85%。由于在德系犹太人中BRCA 1和BRCA 2突变的合并频率超过2%，我们能够估计来自华盛顿，华盛顿特区的一大群犹太男女的癌症风险，方法我们收集了5318名犹太人的血液样本，他们填写了流行病学调查问卷。BRCA 1中185 delAG和5382 insC突变以及BRCA 2中6174 delT突变的携带者通过基于聚合酶链反应的测定来鉴定。我们估计乳腺癌和其他癌症的风险，通过比较的突变和noncarriers.Results的BRCA 1或BRCA 2突变的携带者的亲属的癌症史。到70岁时，携带者患乳腺癌的估计风险为56%（95%置信区间，40%至73%）;卵巢癌为16%（95%置信区间，6%至28%）;前列腺癌为16%（95%置信区间，4%至30%）。BRCA 1突变携带者和BRCA 2突变携带者患乳腺癌的风险没有显著差异，携带者亲属中结肠癌的发病率也没有升高。结论超过2%的德系犹太人携带BRCA 1或BRCA 2突变，增加患乳腺癌、卵巢癌和前列腺癌的风险。乳腺癌的风险可能被高估了，但它们远低于先前基于高风险家庭受试者的估计。(C)1997年，马萨诸塞州医学会。
Background Carriers of germ-line mutations in BRCA1 and BRCA2 from families at high risk for cancer have been estimated to have an 85 percent risk of breast cancer. Since the combined frequency of BRCA1 and BRCA2 mutations exceeds 2 percent among Ashkenazi Jews, we were able to estimate the risk of cancer in a large group of Jewish men and women from the Washington, D.C., area.Methods We collected blood samples from 5318 Jewish subjects who had filled out epidemiologic questionnaires. Carriers of the 185delAG and 5382insC mutations in BRCA1 and the 6174delT mutation in BRCA2 were identified with assays based on the polymerase chain reaction. We estimated the risks of breast and other cancers by comparing the cancer histories of relatives of carriers of the mutations and noncarriers.Results One hundred twenty carriers of a BRCA1 or BRCA2 mutation were identified. By the age of 70, the estimated risk of breast cancer among carriers was 56 percent (95 percent confidence interval, 40 to 73 percent); of ovarian cancer, 16 percent (95 percent confidence interval, 6 to 28 percent); and of prostate cancer, 16 percent (95 percent confidence interval, 4 to 30 percent). There were no significant differences in the risk of breast cancer between carriers of BRCA1 mutations and carriers of BRCA2 mutations, and the incidence of colon cancer among the relatives of carriers was not elevated.Conclusions Over 2 percent of Ashkenazi Jews carry mutations in BRCA1 or BRCA2 that confer increased risks of breast, ovarian, and prostate cancer. The risks of breast cancer may be overestimated, but they fall well below previous estimates based on subjects from high-risk families. (C) 1997, Massachusetts Medical Society.