Potential excess mortality in BRCA1/2 mutation carriers beyond breast, ovarian, prostate, and pancreatic cancers, and melanoma.
Potential excess mortality in BRCA1/2 mutation carriers beyond breast, ovarian, prostate, and pancreatic cancers, and melanoma.
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DOI：
10.1371/journal.pone.0004812
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发表时间：
2009
期刊：
影响因子：
3.7
通讯作者：
Wacholder S
中科院分区：
文献类型：
--
作者：
Mai PL;Chatterjee N;Hartge P;Tucker M;Brody L;Struewing JP;Wacholder S
虽然BRCA 1和BRCA 2突变携带者患乳腺癌、卵巢癌和前列腺癌的风险增加已被广泛研究，但其对死亡率的影响尚未得到很好的量化。此外，尚未研究BRCA突变对非癌症死亡风险的可能影响。在一项对华盛顿地区的德系犹太人进行的基于社区的研究中，我们使用了来自5,287名基因型参与者亲属的死亡率数据，其中120人携带BRCA德系犹太人创始人突变，我们研究了三种德系犹太人BRCA创始人突变与总体和非癌症死亡率风险之间的关联。为了检查这些突变的既定影响之外的风险，我们分析了报告诊断为黑色素瘤和乳腺癌、卵巢癌、前列腺癌和胰腺癌后的死亡和随访时间的数据。使用扩展的亲属队列方法，解释信息删失，我们估计，在没有乳腺癌，卵巢癌，胰腺癌和黑色素瘤的情况下，女性携带者的预期寿命比非携带者低6.8年（95%CI：1.2-10.5）。在男性突变携带者中，在没有前列腺癌和胰腺癌以及黑色素瘤的情况下，预期寿命减少3.7年（95% CI：-0.4，6.8）。当排除任何癌症诊断后的死亡和随访时间时，女性的预期寿命差异为5.7年（95% CI：-0.1，10.4），男性为3.7年（95% CI：-0.4，6.9）。对男性和女性的总体关联性检验显示，BRCA 1/2突变与非癌症死亡率增加之间存在统计学显著相关性（p = 0.024）。 这些发现表明，BRCA 1/2突变对导致老年人死亡的非肿瘤性疾病可能有未知的影响。
Although the increase in risk of developing breast, ovarian, and prostate cancer in BRCA1 and BRCA2 mutation carriers has been studied extensively, its impact on mortality is not well quantified. Further, possible effect of BRCA mutations on non-cancer mortality risk has not been examined. Using mortality data from the relatives of 5,287 genotyped participants, of whom 120 carried a BRCA Ashkenazi Jewish founder mutation, in a community-based study of the Ashkenazi Jewish population in the Washington D.C area, we examined the association between the three Ashkenazi BRCA founder mutations and risk of overall and non-cancer mortality. To examine risks beyond the established effects of these mutations, we analyzed the data excluding both deaths and follow-up times after reported diagnosis of melanoma and cancer of the breast, ovary, prostate, and pancreas. Using an extension of the kin-cohort method that accounts for informative censoring, we estimated that, in the absence of breast, ovarian, and pancreatic cancers, and melanoma, female carriers had a life expectancy that was 6.8 years lower (95% CI: 1.2–10.5) than non-carriers. In male mutation carriers, the reduction in life expectancy, in the absence of prostate and pancreatic cancers and melanoma, was 3.7 (95% CI: −0.4, 6.8) years. When deaths and follow-up times after any cancer diagnosis were excluded, the difference in life expectancy was 5.7 years for women (95% CI: −0.1, 10.4) and 3.7 years for men (95% CI: −0.4, 6.9). An overall test of association for men and women together showed a statistically significant association between BRCA1/2 mutations and increased non-cancer mortality (p = 0.024). These findings suggest that there may be unknown effects of BRCA1/2 mutations on non-neoplastic diseases that cause death at older ages.
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影响因子：
10.3
作者：
Risch, Harvey A.;McLaughlin, John R.;Narod, Steven A.
通讯作者：
Narod, Steven A.
DOI：
10.1093/jnci/94.18.1365
发表时间：
2002-09-18
期刊：
JOURNAL OF THE NATIONAL CANCER INSTITUTE
影响因子：
--
作者：
Brose, MS;Rebbeck, TR;Weber, BL
通讯作者：
Weber, BL
影响因子：
6.2
作者：
Cass, I;Baldwin, RL;Karlan, BY
通讯作者：
Karlan, BY
影响因子：
158.5
作者：
Struewing, JP;Hartge, P;Tucker, MA
通讯作者：
Tucker, MA
亲属队列估算中的竞争风险调整
影响因子：
2.1
作者：
Chatterjee, N;Hartge, P;Wacholder, S
通讯作者：
Wacholder, S