Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations.
Associations of high-grade prostate cancer with BRCA1 and BRCA2 founder mutations.
复制标题
DOI：
10.1158/1078-0432.ccr-08-1822
复制
发表时间：
2009-02-01
期刊：
影响因子：
--
通讯作者：
Burk RD
中科院分区：
文献类型：
--
作者：
Agalliu I;Gern R;Leanza S;Burk RD
BRCA 1，特别是BRCA 2基因中的蛋白质截短突变与前列腺癌相关。然而，与Gleason评分、前列腺癌家族史、乳腺癌家族史和卵巢癌家族史的关联程度仍不确定。为了进一步研究位于BRCA 1（185 delAG，5382 insC）或BRCA 2（6174 delT）基因中的三种创始突变与前列腺癌之间的关联，我们在德系犹太男性中进行了一项研究，包括979例前列腺癌病例和1,251例对照。获得了前列腺癌病理学、诊断时年龄和所有癌症家族史的详细信息。使用逻辑回归模型估计比值比（OR）和95%置信区间（CI）。BRCA 2突变携带者的前列腺癌风险增加（OR，1.9; 95% CI 0.9-4.1），但BRCA 1突变携带者则无此风险。BRCA 2突变携带者Gleason评分为7 - 10时的OR为3.2（95% CI，1.4-7.3），但Gleason评分<7时未观察到相关性。BRCA 1 - 185 delAG突变携带者的Gleason评分≥7肿瘤的OR也为3.5（95% CI，1.2-10.3）;然而，BRCA 1 - 185 delAG或5382 insC突变的相关性无统计学显著性。在没有乳腺癌和/或卵巢癌一级家族史的男性中，创始人突变与前列腺癌之间的关联更强，但不受前列腺癌家族史的影响。这些结果表明，BRCA 2创始人突变使高级别前列腺癌的风险增加3倍。虽然BRCA 1突变与前列腺癌无关，但BRCA 1 - 185 delAG与高Gleason评分肿瘤相关。在遗传咨询和/或评估治疗方案时应仔细考虑这些发现。
Protein-truncating mutations in BRCA1 and in particular BRCA2 genes have been associated with prostate cancer. However, there is still uncertainty about the magnitude of association particularly with Gleason score, and family history of prostate, breast, and ovary cancers. To further examine associations between three founder mutations located in BRCA1 (185delAG, 5382insC) or BRCA2 (6174delT) genes and prostate cancer, we conducted a study of 979 prostate cancer cases and 1,251 controls among Ashkenazi Jewish men. Detailed information was obtained on prostate cancer pathology, age at diagnosis, and family history of all cancers. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using logistic regression models. Prostate cancer risk was increased (OR, 1.9; 95% CI 0.9-4.1) for BRCA2 mutation carriers but not for BRCA1 mutation carriers. BRCA2 mutation carriers had an OR of 3.2 (95% CI, 1.4-7.3) for Gleason score of 7 to 10, but no association was observed for Gleason score of <7. Carriers of BRCA1-185delAG mutation also had an OR of 3.5 (95% CI, 1.2-10.3) for Gleason score of ≥7 tumors; however, the association of either BRCA1-185delAG or 5382insC mutation was not statistically significant. Associations between founder mutations and prostate cancer were stronger in men with no first-degree family history of breast and/or ovarian cancers but were unaffected by family history of prostate cancer. These results indicate that the BRCA2 founder mutation confers a 3-fold elevated risk of high-grade prostate cancer. Although BRCA1 mutations were not associated with prostate cancer, the BRCA1-185delAG was associated with high Gleason score tumors. These findings should be carefully considered in genetic counseling and/or evaluating therapeutic options.