Germline BRCA1 mutations increase prostate cancer risk.
Germline BRCA1 mutations increase prostate cancer risk.
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DOI：
10.1038/bjc.2012.146
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发表时间：
2012-05-08
影响因子：
8.8
通讯作者：
Kote-Jarai, Z.
中科院分区：
文献类型：
--
作者：
Leongamornlert, D.;Mahmud, N.;Tymrakiewicz, M.;Saunders, E.;Dadaev, T.;Castro, E.;Goh, C.;Govindasami, K.;Guy, M.;O'Brien, L.;Sawyer, E.;Hall, A.;Wilkinson, R.;Easton, D.;Goldgar, D.;Eeles, R.;Kote-Jarai, Z.
前列腺癌(PrCa)是影响男性的最常见的癌症之一，但其病因尚不清楚。PrCA的家族史，特别是在年轻时，是一个强烈的危险因素。此前有报道称，女性乳腺癌家族中男性BRCA1突变携带者的PrCa风险增加，但这种风险是否得到证实存在争议。我们试图通过在一个大的英国人群样本集中进行候选基因研究来评估生殖系BRCA1突变在PrCA易感性中的作用。我们对913例年龄在36-86岁之间的患者进行了BRCA1胚系突变筛查，研究内容丰富了发病年龄较早的患者。我们用Sanger测序法分析了BRCA1基因的整个编码区。多重连接依赖的探针扩增也被用来评估460例大重排的频率。我们鉴定了4个有害突变和45个未分类的变种(UV)。本研究中恶性突变的频率为0.45%，其中3名突变携带者在65岁时发病，1名⩽携带者在69岁发病。使用之前估计的人群携带者频率，有害的BRCA1突变使∼的PrCA相对风险增加3.75倍(95%可信区间1.02-9.6)，在65岁时转化为8.6%的累积风险。这项研究表明，BRCA1基因种系突变的男性患PrCA的风险增加。这可能对可能的筛查战略和有针对性的治疗产生重大影响。
Prostate cancer (PrCa) is one of the most common cancers affecting men but its aetiology is poorly understood. Family history of PrCa, particularly at a young age, is a strong risk factor. There have been previous reports of increased PrCa risk in male BRCA1 mutation carriers in female breast cancer families, but there is a controversy as to whether this risk is substantiated. We sought to evaluate the role of germline BRCA1 mutations in PrCa predisposition by performing a candidate gene study in a large UK population sample set. We screened 913 cases aged 36–86 years for germline BRCA1 mutation, with the study enriched for cases with an early age of onset. We analysed the entire coding region of the BRCA1 gene using Sanger sequencing. Multiplex ligation-dependent probe amplification was also used to assess the frequency of large rearrangements in 460 cases. We identified 4 deleterious mutations and 45 unclassified variants (UV). The frequency of deleterious BRCA1 mutation in this study is 0.45% three of the mutation carriers were affected at age ⩽65 years and one developed PrCa at 69 years. Using previously estimated population carrier frequencies, deleterious BRCA1 mutations confer a relative risk of PrCa of ∼3.75-fold, (95% confidence interval 1.02–9.6) translating to a 8.6% cumulative risk by age 65. This study shows evidence for an increased risk of PrCa in men who harbour germline mutations in BRCA1. This could have a significant impact on possible screening strategies and targeted treatments.
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影响因子：
14.8
作者：
Kumar, Prateek;Henikoff, Steven;Ng, Pauline C.
通讯作者：
Ng, Pauline C.
影响因子：
8
作者：
Mancini, DN;Rodenhiser, DI;Archer, TK
通讯作者：
Archer, TK
影响因子：
2.2
作者：
Diez, Orland;Gutierrez-Enriquez, Sara;Balmana, Judith
通讯作者：
Balmana, Judith
影响因子：
3.4
作者：
Al-Mulla F;Bland JM;Serratt D;Miller J;Chu C;Taylor GT
通讯作者：
Taylor GT
影响因子：
6.6
作者：
GRONBERG, H;DAMBER, L;DAMBER, JE
通讯作者：
DAMBER, JE