西班牙國立癌癥研究中心（CNIO）下屬的前列腺癌和生殖泌尿系腫瘤臨床研究部門的最新研究結(jié)果發(fā)現(xiàn),與一般的前列腺癌患者相比,前列腺癌患者如果同時發(fā)生BRCA2基因變異,就會出現(xiàn)不良的預(yù)后及很低的生存機率.
Olmos是前列腺癌和生殖泌尿系腫瘤臨床研究部門的領(lǐng)導(dǎo)人,他說：“大部分前列腺癌患者都有良好的預(yù)后,在日常臨床實踐中,我們所面臨的最大的挑戰(zhàn)就是很難確定哪些患者病情是致命的.”
為了尋找與病情發(fā)展有關(guān)的遺傳標(biāo)記,本研究的作者對61名前列腺癌患者進(jìn)行了檢測,這些患者同時伴有BRCA2基因
（該基因能抑制腫瘤生長,對DNA具有保護(hù)作用）變異,18名患者伴有BRCA1基因（該基因的功能與BRCA2的相似）變異,
本研究排除了兩個基因同時發(fā)生突變的1,940名患者.
這是目前調(diào)查前列腺癌患者BRCA1或BRCA2基因突變規(guī)模最大的一項研究,；這些基因與家族性乳腺癌和卵巢癌綜合征有關(guān).
調(diào)查結(jié)果顯示,BRCA1和BRCA2發(fā)生變異的患者,其前列腺癌都發(fā)展得比較嚴(yán)重,而且還有轉(zhuǎn)移的跡象.
甚至,在同一組沒有檢測到癌細(xì)胞轉(zhuǎn)移的患者中,伴有基因突變的23%的患者在未來5年內(nèi)會發(fā)生癌細(xì)胞轉(zhuǎn)移,而基因正常的患者只有7%的會出現(xiàn)這種情況.在診斷的5年后,19% BRCA2基因突變攜帶者在癌癥早期就死亡,而在基因正常的患者中,這種死亡率只有4%.BRCA1基因突變在這方面的差異不顯著.
文章的第一作者Castro說：“這些數(shù)據(jù)表明,BRCA2是第一個可用于前列腺癌預(yù)后的遺傳因子.”她還補充說：“本研究的結(jié)果表明,需要轉(zhuǎn)變對伴有BRCA基因突變的前列腺癌患者的臨床治療管理.目前的治療標(biāo)準(zhǔn)對于此類患者來說似乎是不足夠的,而且沒有具體的行動指南.”
“既然我們已經(jīng)可以設(shè)法確定具有潛在致命疾病的患者,我們的下一個挑戰(zhàn)就是尋找最有效而且副作用最少的治療方法.”Olmos說.
前列腺癌是世界上第二個最常見的男性癌癥類型,發(fā)達(dá)國家,它是最見的腫瘤疾病.
在過去的幾十年里,由于人的壽命都有所延長以及前列腺特異性抗原（Prostate-Specific Antigen,PSA）的廣泛使用,使得這種癌癥的發(fā)生有上升的趨勢.有幸的是,由這種癌癥所引起的死亡率在下降,這都?xì)w功于發(fā)病早期的診斷以及治療方式的改良.
雖然如此,有些情況仍有致命的危險,需要努力尋找到能識別預(yù)后不良的患者的資源,建立更合適的治療策略.（生物谷Bioon.com）
doi: 10.1200/JCO.2012.43.1882
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Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer
Elena Castro,Chee Goh,David Olmos?,Ed Saunders,Daniel Leongamornlert,Malgorzata Tymrakiewicz,Nadiya Mahmud,Tokhir Dadaev,Koveela Govindasami,Michelle Guy,Emma Sawyer,Rosemary Wilkinson,Audrey Ardern-Jones,Steve Ellis,Debra Frost,Susan Peock,D. Gareth Evans,Marc Tischkowitz,Trevor Cole,Rosemarie Davidson,Diana Eccles,Carole Brewer,Fiona Douglas,Mary E. Porteous,Alan Donaldson,Huw Dorkins,Louise Izatt,Jackie Cook,
Shirley Hodgson,M. John Kennedy,Lucy E. Side,Jacqueline Eason,Alex Murray,Antonis C. Antoniou,Douglas F. Easton,Zsofia Kote-Jarai and Rosalind Eeles
Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes.
Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1).
Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup.
Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.
