Hereditary breast cancer in Jews.
Hereditary breast cancer in Jews.
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DOI：
10.1007/s10689-004-9550-2
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发表时间：
2004-01-01
期刊：
影响因子：
2.2
通讯作者：
Rubinstein, Wendy S
中科院分区：
文献类型：
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作者：
Rubinstein, Wendy S
有乳腺癌家族史的犹太妇女比非犹太妇女风险更高，特别是早发性乳腺癌。这似乎在很大程度上是由于德系犹太人中三种BRCA1和BRCA2创始人突变的高患病率（2.5%）。大约4%至8%的非犹太男性乳腺癌病例与19%的犹太男性乳腺癌病例携带生殖系BRCA突变。犹太妇女一生中受BRCA突变的影响不成比例，在任何年龄诊断出乳腺癌的携带率为10%，在40岁诊断出乳腺癌的携带率为21%至30%。在非犹太人中，50岁之前诊断出乳腺癌的比例为6.1%。基于先证者基因分型的终生患病率估计在犹太人和非犹太人人群中差异很大。然而，一项对1008名患有乳腺癌的犹太妇女进行的研究将基因分型扩展到亲属，发现高转移率的标准误差相当小。这项研究和对非犹太人早发性乳腺癌的研究发现，仅通过家族史筛查，至少有一半的高危病例会被遗漏。虽然非犹太人的携带率太低，不能考虑基因筛查，但德系犹太人的携带率很高，基因筛查的技术障碍较少。德系犹太人BRCA创始人突变的高遗传可归因癌症风险，卵巢癌和早发性乳腺癌的致命性，以及医疗干预措施有效性的日益明确，使得进一步的对话和研究势在必行，以保持遗传筛查的指导方针最新。
A family history of breast cancer poses higher risks for Jewish versus non-Jewish women, particularly for early-onset breast cancer. This appears to be due in large part to the high prevalence (2.5%) of three BRCA1 and BRCA2 founder mutations in Ashkenazi Jews. About 4 to 8% of non-Jewish male breast cancer cases versus 19% of Jewish male breast cancer cases carry germline BRCA mutations. Jewish women are disproportionately impacted by BRCA mutations throughout life, with a 10% carrier rate for breast cancer diagnosed at any age and a 21 to 30% carrier rate for breast cancer diagnosed by age 40. Comparable rates in non-Jewish populations are 6.1% for breast cancer diagnosed before age 50. Lifetime penetrance estimates based on genotyping of probands have ranged widely in Jewish and non-Jewish populations. However, a study of 1008 Jewish women with breast cancer which extended genotyping to relatives found high penetrance rates with considerably smaller standard errors. This study and studies of early-onset incident breast cancer in non-Jews have found that at least half of high-risk cases would be missed by family history screening alone. While the carrier rate in non-Jewish populations is too low to consider genetic screening, the carrier rate in Ashkenazi Jews is high and genetic screening poses fewer technical barriers. The high genetic attributable cancer risks of Ashkenazi BRCA founder mutations, the sobering lethality of ovarian and early onset breast cancers, and the increasing clarity about effectiveness of medical interventions make imperative further dialogue and research to keep guidelines for genetic screening up to date.