携带BRCA2基因突变者的前列腺癌进展与生存情况

Prostate cancer progression and survival in BRCA2 mutation carriers.

作者信息

Tryggvadóttir Laufey, Vidarsdóttir Linda, Thorgeirsson Tryggvi, Jonasson Jon Gunnlaugur, Olafsdóttir Elinborg Jona, Olafsdóttir Gudridur Helga, Rafnar Thorunn, Thorlacius Steinunn, Jonsson Eirikur, Eyfjord Jorunn Erla, Tulinius Hrafn

机构信息

Icelandic Cancer Registry, PO Box 5420, Iceland.

出版信息

J Natl Cancer Inst. 2007 Jun 20;99(12):929-35. doi: 10.1093/jnci/djm005. Epub 2007 Jun 12.

DOI:10.1093/jnci/djm005

PMID:17565157

Abstract

BACKGROUND

Mutations in the BRCA2 gene are associated with an increased risk of prostate cancer, but it is not known whether they are associated with progression of the disease. We compared prostate cancer-specific survival, disease stage, and tumor grade between prostate cancer patients carrying the Icelandic BRCA2 999del5 founder mutation and noncarriers.

METHODS

Using population-based registries, we identified all 596 prostate cancer patients who were diagnosed in Iceland during 1955 through 2004 among 29603 male relatives of unselected breast cancer probands. BRCA2 mutation status could be determined for 527 patients (88.4%). Stage and grade were abstracted from original records, blindly with respect to mutation status, for a subgroup of 89 patients that included all mutation carriers and, for each carrier, two control patients without the BRCA2 999del5 mutation who were matched to the carrier on years of diagnosis and birth. Hazard ratios (HRs) and 95% confidence intervals (CIs) for prostate cancer-specific survival were estimated using multivariable regression models. All statistical tests were two-sided.

RESULTS

The mutation was carried by 30 patients (5.7%). Compared with noncarriers, BRCA2 999del5 mutation carriers had a lower mean age at diagnosis (69.0 years versus 74.0 years; P = .002), more advanced tumor stage (stages 3 or 4, 79.3% versus 38.6%; P < .001), higher tumor grade (grades G3-4, 84.0% versus 52.7%, P = .007), and shorter median survival time (2.1 years, 95% CI = 1.4 to 3.6 years, versus 12.4 years, 95% CI = 9.9 to 19.7 years). Carrying the BRCA2 999del5 mutation was also associated with an increased risk of dying from prostate cancer (adjusting for year of diagnosis and birth, HR = 3.42, 95% CI = 2.12 to 5.51); the association remained after adjustment for stage and grade (HR = 2.35, 95% CI = 1.08 to 5.11). The prognosis of BRCA2 999del5 mutation carriers was not associated with period of diagnosis or with relatedness to breast cancer probands.

CONCLUSIONS

The Icelandic BRCA2 999del5 founder mutation was strongly associated with rapidly progressing lethal prostate cancer.

摘要

背景

BRCA2基因的突变与前列腺癌风险增加相关，但尚不清楚它们是否与疾病进展有关。我们比较了携带冰岛BRCA2基因999del5始祖突变的前列腺癌患者与未携带者之间的前列腺癌特异性生存率、疾病分期和肿瘤分级。

方法

利用基于人群的登记系统，我们在29603名未经选择的乳腺癌先证者的男性亲属中，识别出1955年至2004年期间在冰岛被诊断出的所有596例前列腺癌患者。527例患者（88.4%）的BRCA2突变状态可被确定。对于包括所有突变携带者以及针对每位携带者选取的两名与携带者在诊断年份和出生年份相匹配、但不携带BRCA2基因999del5突变的对照患者组成的89例患者亚组，从原始记录中提取分期和分级信息，提取过程对突变状态不知情。使用多变量回归模型估计前列腺癌特异性生存的风险比（HRs）和95%置信区间（CIs）。所有统计检验均为双侧检验。

结果

30例患者（5.7%）携带该突变。与未携带者相比，BRCA2基因999del5突变携带者的诊断时平均年龄较低（69.0岁对74.0岁；P = 0.002），肿瘤分期更晚（3期或4期，79.3%对38.6%；P < 0.001），肿瘤分级更高（G3 - 4级，84.0%对52.7%，P = 0.007），中位生存时间更短（2.1年，95% CI = 1.4至3.6年，对12.4年，95% CI = 9.9至19.7年）。携带BRCA2基因999del5突变还与死于前列腺癌的风险增加相关（校正诊断年份和出生年份后，HR = 3.42，95% CI = 2.12至5.51）；在校正分期和分级后，该关联仍然存在（HR = 2.35，95% CI = 1.08至5.11）。BRCA2基因999del5突变携带者的预后与诊断时期或与乳腺癌先证者的亲缘关系无关。