有3名或3名以上親屬患這種病再加上基因突變會(huì)提高侵襲性前列腺癌的風(fēng)險(xiǎn),。
近日,，美國(guó)人類遺傳學(xué)會(huì)于波士頓舉行,，年會(huì)上報(bào)告的一項(xiàng)研究說(shuō),，患前列腺癌的男性有3名或者更多的患前列腺癌的親屬,，而這些男性的8個(gè)DNA修復(fù)基因之中如果有1個(gè)發(fā)生了突變,，那么他們就可能出現(xiàn)侵襲性的前列腺癌,。
“在我們研究的22個(gè)DNA修復(fù)基因中，我們發(fā)現(xiàn)了其中8個(gè)基因的14種失去了功能的變種,；這導(dǎo)致蛋白質(zhì)不能完全發(fā)揮作用,。在我們的研究中，攜帶了這些類型的基因突變的男性與沒(méi)有攜帶這些突變的男性相比,，他們患轉(zhuǎn)移性前列腺癌的幾率要顯著更高,，”報(bào)告了這項(xiàng)研究的英國(guó)癌癥研究所的研究生Daniel Leongamornlert說(shuō)。
該研究讓參與英國(guó)遺傳前列腺癌研究項(xiàng)目的大約200名患家族前列腺癌的英國(guó)男性參與其中。Leongamornlert和他在英國(guó)癌癥研究所（ICR）的同事搜索了為參與DNA修復(fù)路徑的蛋白質(zhì)編碼的22個(gè)基因的遺傳突變的序列,。
這組科研人員在前列腺癌病人的血樣DNA序列中發(fā)現(xiàn)了14種失去功能的基因變種,。在BRCA2腫瘤抑制基因中發(fā)現(xiàn)了4個(gè)突變。這些科學(xué)家還在另一種腫瘤抑制基因BRCA1以及另外6種已知在DNA修復(fù)中發(fā)揮作用的基因中發(fā)現(xiàn)了突變,。這些基因分別是：ATM,，CHEK2，BRIP1,，MUTYH,，PALB2 和PMS2。其中幾個(gè)DNA修復(fù)基因的突變與其他類型的癌癥有聯(lián)系,。
“擁有失去功能的突變的DNA修復(fù)基因帶來(lái)了4.64 的前列腺癌高相對(duì)風(fēng)險(xiǎn),。這些新發(fā)現(xiàn)的罕見(jiàn)基因變種可能作為開(kāi)發(fā)藥物的靶標(biāo)，用于出現(xiàn)侵襲性前列腺癌的風(fēng)險(xiǎn)高的前列腺癌男性病人,，”英國(guó)癌癥研究所（ICR）領(lǐng)導(dǎo)了這項(xiàng)研究的資深科學(xué)家Zsofia Kote-Jarai博士說(shuō),。
“這些發(fā)現(xiàn)可能在實(shí)施家族前列腺癌的新型篩查和治療策略方面有臨床用途，” 該研究的資深作者,、英國(guó)癌癥研究所（ICR）腫瘤遺傳學(xué)研究組組長(zhǎng),、腫瘤遺傳學(xué)教授Rosalind Eeles M.D.補(bǔ)充說(shuō)。Eeles博士還是英國(guó)遺傳前列腺癌研究項(xiàng)目的創(chuàng)始人和研究組長(zhǎng),，該研究是在1993年建立的,，有170家醫(yī)院參與。
這組科學(xué)家在美國(guó)人類遺傳學(xué)會(huì)上公布的論文摘要的題目是《家族前列腺癌病例的DNA修復(fù)基因的常見(jiàn)種系突變》,。(生物谷Bioon.com)
生物谷推薦的英文摘要
American Society of Human Genetics
http://www.ashg.org/2013meeting/abstracts/fulltext/f130120218.htm
Frequent germline mutations in DNA repair genes in familial prostate cancer cases
D. Leongamornlert, E. Saunders, T. Dadaev, M. Tymrakiewicz, C. Goh, S. Jugurnauth-Little, I. Kozarewa, K. Fenwick, I. Assiotis, D. Barrowdale, K. Govindasami, M. Guy, E. Sawyer, R. Wilkinson, A. Antoniou3, R. Eeles, Z. Kote-Jarai
Prostate cancer (PrCa) is one of the most common diseases to affect men worldwide and the underlying aetiology is poorly understood compared with other complex diseases. Many common variants have been identified over the last few years which are associated with PrCa risk but very few rare, higher risk alleles have been found. To investigate if rare variants in 22 DNA repair genes have a role in PrCa predisposition, we analysed these genes in a UK collection of familial prostate cancer cases. Germline DNA samples were obtained from 191 PrCa cases which had 3 or more relatives affected with PrCa. These samples were deeply re-sequenced using Agilent Sureselect target capture and Illumina HiSeq systems. The exonic and intronic sequences of 22 tumour suppressor DNA repair genes were analysed for genomic variation using a pipeline consisting of BWA, GATK and Annovar. We identified 14 loss-of-function (LoF) mutations (7.3%) with the highest fraction contributed by BRCA2 (4 mutations). Mutations were also found in ATM, CHEK2, BRIP1, BRCA1, MUTYH, PALB2 and PMS2. In addition, 13 missense variants which are likely to modify protein function were also identified. LoF mutation carriers had significantly higher odds of nodal involvement, metastasis or death from PrCa OR 11.32 (95% CI: 2.27-69.56; P=0.00421). Using a modified segregation analysis approach, we estimate that LoF mutations in any of the studied genes confer a relative risk of PrCa of 4.64, (95% confidence interval 3.84-5.61). In summary we present evidence that mutations in DNA repair genes may have a significant role in familial PrCa predisposition and that carriers of LoF mutations in these genes are more likely to have aggressive disease. This may have clinical utility in the implementation of new screening and treatment strategies.
