The G84E mutation of HOXB13 is associated with increased risk for prostate cancer: results from the REDUCE trial
The G84E mutation of HOXB13 is associated with increased risk for prostate cancer: results from the REDUCE trial
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DOI：
10.1093/carcin/bgt055
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发表时间：
2013-06-01
期刊：
影响因子：
4.7
通讯作者：
Xu, Jianfeng
中科院分区：
文献类型：
--
作者：
Chen, Zhuo;Greenwood, Celia;Xu, Jianfeng
据报道，一种新的罕见突变，同源框B13（HOXB 13）G84 E，在遗传性前列腺癌（PCa）家族中与PCa共分离，并与无关病例和对照中的PCa风险相关。在这项研究中，我们的目的是比较G84 E突变频率的不同种族/民族的受试者在世界上不同的地理区域，并评估其发展PCa的风险，在减少前列腺癌事件的度他雄胺（REDUCE）试验。所有3508例受试者的初始前列腺活检均为阴性，并在第2年和第4年进行活检以检测PCa。仅在高加索人中检测到G84 E突变，携带者频率最高的是北方欧洲（1.06%），其次是西欧（0.60%）和北美（0.31%）。在南欧、东欧、拉丁美洲、澳大利亚和南非没有观察到突变携带者。在白人中，G84 E突变频率在阳性和阴性活检受试者中分别为0.99%和0.24%（P 0.01）。在阳性活检受试者中，有阳性家族史的受试者的频率显著高于无阳性家族史的受试者（4.31% vs 0.34%，P 0.002）。随访4年，13例突变携带者PCa检出率为53.8%，3186例非携带者PCa检出率为22.0%，相对危险度为2.45（95%可信区间为1.484.07）。所有突变携带者都有一个共同的单倍型，这表明了奠基者效应。在芬兰，G84 E突变估计发生在1792年（95%可信区间：1735 - 1831）。总之，HOXB 13的G84 E突变，一种可能发生在北方欧洲的相对较新的突变，显著增加了PCa的风险。
A novel rare mutation, homeobox B13 (HOXB13) G84E, was reported to co-segregate with prostate cancer (PCa) in hereditary PCa families and associate with PCa risk in unrelated cases and controls. In this study, we aim to compare the G84E mutation frequency among subjects of different races/ethnicities from various geographic regions in the world and to assess its risk for developing PCa, in the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial. All the 3508 subjects had initial negative prostate biopsy and were biopsied at Year 2 and 4 for detection of PCa. The G84E mutation was detected only in Caucasians, with the highest carrier frequency in Northern Europe (1.06%), followed by Western Europe (0.60%) and North America (0.31%). No mutation carrier was observed in Southern Europe, Eastern Europe, Latin America, Australia and South Africa. In Caucasians, the G84E mutation frequency was 0.99% and 0.24% in positive and negative biopsy subjects, respectively (P 0.01). In positive biopsy subjects, the frequency was significantly higher in subjects with a positive family history than those without (4.31% versus 0.34%, P 0.002). In the 4 year follow-up, the PCa detection rate was 53.8% among the 13 mutation carriers and 22.0% among 3186 non-carriers, relative risk 2.45 (95% confidence interval: 1.484.07). All mutation carriers shared a common haplotype, suggesting a founder effect. In Finland, the G84E mutation was estimated to occur in the year 1792 (95% credible interval: 17351831). In conclusion, the G84E mutation of HOXB13, a relatively recent mutation that likely occurred in Northern Europe, significantly increases risk for PCa.