Sigurdsson S, Thorlacius S, Tomasson J, Tryggvadottir L, Benediktsdottir K, Eyfjörd J E, Jonsson E
Molecular and Cell Biology Research Laboratory, Icelandic Cancer Society, Reykjavik.
J Mol Med (Berl). 1997 Oct;75(10):758-61. doi: 10.1007/s001090050162.
Molecular genetic analysis of prostate cancer has gained considerable attention in recent years. The hope is to find genetic markers that can help to determine which patients are likely to develop a progressive or lethal disease and would therefore benefit from early treatment. The BRCA2 gene on chromosome 13 has been associated with familial male and female breast cancer. A founder mutation in this gene has been detected in the Icelandic population. This is a 5-bp deletion that leads to an early termination and truncated protein. Clustering of prostate cancers in some of the Icelandic BRCA2 families implies that mutation carriers are at increased risk of developing cancer of the prostate. The aim of the study was to investigate this mutation in Icelandic prostate cancer patients related to BRCA2 positive breast cancer probands and to estimate the prevalence of this mutation in unselected prostate cancer patients. To examine the potential role of this mutation in prostate cancer we analyzed prostate cancer cases from 16 BRCA2 families and all available samples from individuals diagnosed with prostate cancer in Iceland over a period of 1 year. The risk ratio of prostate cancer was 4.6 (1.9-8.8) in first-degree relatives and 2.5 (1.2-4.6) in second-degree relatives of the 16 BRCA2 positive breast cancer probands. Of 26 prostate cancer cases found in these families 12 were analyzed, and 8 of these (66.7%) had the BRCA2 mutation. All of these patients developed an advanced disease, and all have died of prostate cancer (median survival 22.5 months). Among unselected cases 3.1% (2/65) had the mutation and developed an advanced disease as well. This specific mutation in the BRCA2 gene is found in a subset of Icelandic prostate cancer cases and appears to be a marker for poor prognosis.
近年来，前列腺癌的分子遗传学分析受到了广泛关注。人们希望找到能够帮助确定哪些患者可能会发展为进展性或致命性疾病，从而从早期治疗中获益的遗传标记。位于13号染色体上的BRCA2基因与家族性男性和女性乳腺癌有关。在冰岛人群中检测到了该基因的一个始祖突变。这是一个5碱基对的缺失，导致早期终止和截短的蛋白质。冰岛一些BRCA2家族中前列腺癌的聚集现象表明，突变携带者患前列腺癌的风险增加。本研究的目的是调查冰岛前列腺癌患者中与BRCA2阳性乳腺癌先证者相关的这种突变，并估计未选择的前列腺癌患者中这种突变的患病率。为了研究这种突变在前列腺癌中的潜在作用，我们分析了来自16个BRCA2家族的前列腺癌病例以及冰岛在1年时间内所有被诊断为前列腺癌的个体的可用样本。16名BRCA2阳性乳腺癌先证者的一级亲属患前列腺癌的风险比为4.6（1.9 - 8.8），二级亲属为2.5（1.2 - 4.6）。在这些家族中发现的26例前列腺癌病例中，对12例进行了分析，其中8例（66.7%）有BRCA2突变。所有这些患者都发展为晚期疾病，并且都死于前列腺癌（中位生存期22.5个月）。在未选择的病例中，3.1%（2/65）有该突变并且也发展为晚期疾病。BRCA2基因中的这种特定突变在冰岛前列腺癌病例的一个子集中被发现，似乎是预后不良的一个标记。
