BRCA mutations and risk of prostate cancer in Ashkenazi Jews
BRCA mutations and risk of prostate cancer in Ashkenazi Jews
复制标题
DOI：
10.1158/1078-0432.ccr-03-0604
复制
发表时间：
2004-05-01
影响因子：
11.5
通讯作者：
Offit, K
中科院分区：
文献类型：
--
作者：
Kirchhoff, T;Kauff, ND;Offit, K
目的：乳腺癌连锁联盟和其他以家庭为基础的调查表明，BRCA突变的男性携带者患前列腺癌的风险增加。几个研究前列腺癌患者BRCA突变频率的系列研究没有证实这一发现。为了澄清这个问题，我们进行了一个大型的病例对照研究。实验设计：血液标本从251个德系犹太人前列腺癌的存在下，三个常见的德系犹太人的创始人突变BRCA 1和BRCA 2进行了筛选。创始人突变的发病率进行了比较，创始人突变的发病率在1472男性德系犹太人志愿者没有前列腺癌采用logistic回归分析后调整age.Results：十三（5.2%）例BRCA 1或BRCA 2与28（1.9%）对照组相比，有一个有害的突变。校正年龄后，BRCA 1或BRCA 2突变的存在与前列腺癌的发生相关（比值比，3.41; 95%置信区间，1.64-7.06; P = 0.001）。当结果按基因分层时，BRCA 2突变携带者表现出前列腺癌的风险增加（比值比，4.78; 95%置信区间，1.87-12.25; P = 0.001），而在BRCA 1突变携带者的风险没有显着increasing.Conclusions：BRCA 2突变是更有可能被发现在前列腺癌患者中比年龄匹配的控制。这些结果支持BRCA 2有害突变与前列腺癌风险增加相关的假设。
Purpose: The Breast Cancer Linkage Consortium and other family-based ascertainments have suggested that male carriers of BRCA mutations are at increased risk of prostate cancer. Several series looking at the frequency of BRCA mutations in unselected patients with prostate cancer have not confirmed this finding. To clarify this issue, we conducted a large case-control study.Experimental Design: Blood specimens from 251 unselected Ashkenazi men with prostate cancer were screened for the presence of one of the three common Ashkenazi founder mutations in BRCA1 and BRCA2. The incidence of founder mutations was compared with the incidence of founder mutations in 1472 male Ashkenazi volunteers without prostate cancer using logistic regression analysis after adjusting for age.Results: Thirteen (5.2%) cases had a deleterious mutation in BRCA1 or BRCA2 compared with 28 (1.9%) controls. After adjusting for age, the presence of a BRCA1 or BRCA2 mutation was associated with the development of prostate cancer (odds ratio, 3.41; 95% confidence interval, 1.64-7.06; P = 0.001). When results were stratified by gene, BRCA2 mutation carriers demonstrated an increased risk of prostate cancer (odds ratio, 4.78; 95% confidence interval, 1.87-12.25; P = 0.001), whereas the risk in BRCA1 mutation carriers was not significantly increased.Conclusions: BRCA2 mutations are more likely to be found in unselected individuals with prostate cancer than age-matched controls. These results support the hypothesis that deleterious mutations in BRCA2 are associated with an increased risk of prostate cancer.