Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database.
Cancer incidence and survival in Lynch syndrome patients receiving colonoscopic and gynaecological surveillance: first report from the prospective Lynch syndrome database.
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DOI：
10.1136/gutjnl-2015-309675
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发表时间：
2017-03
期刊：
影响因子：
24.5
通讯作者：
Mallorca Group (http://mallorca-group.eu)
中科院分区：
文献类型：
--
作者：
Møller P;Seppälä T;Bernstein I;Holinski-Feder E;Sala P;Evans DG;Lindblom A;Macrae F;Blanco I;Sijmons R;Jeffries J;Vasen H;Burn J;Nakken S;Hovig E;Rødland EA;Tharmaratnam K;de Vos Tot Nederveen Cappel WH;Hill J;Wijnen J;Green K;Lalloo F;Sunde L;Mints M;Bertario L;Pineda M;Navarro M;Morak M;Renkonen-Sinisalo L;Frayling IM;Plazzer JP;Pylvanainen K;Sampson JR;Capella G;Mecklin JP;Möslein G;Mallorca Group (http://mallorca-group.eu)
林奇综合征的癌症风险和监测效果的估计一直存在偏倚，部分原因是依赖于回顾性研究。我们试图在接受前瞻性癌症监测的患者中建立更可靠的估计。我们对携带影响MLH 1、MSH 2、MSH 6或PMS 2的Lynch综合征相关突变的患者进行了一项多中心研究。在Oracle关系数据库中整理了关于监测、癌症和结果的标准化信息，并按年龄、性别和突变基因进行了分析。对1942名既往无癌症的突变携带者进行了随访，包括结肠镜监测，为期13782观察年。 314例患者发生癌症，主要是结直肠癌（n=151）、子宫内膜癌（n=72）和卵巢癌（n=19）。MLH 1和MSH 2突变携带者从25岁起就被检测到癌症，MSH 6和PMS 2携带者从大约40岁起就被检测到癌症。 在每例患者中检测到的首次癌症中，MLH 1、MSH 2、MSH 6和PMS 2突变携带者在70年时的结直肠癌累积发病率分别为46%、35%、20%和10%。 子宫内膜癌的等效累积发病率分别为34%、51%、49%和24%;卵巢癌的等效累积发病率分别为11%、15%、0%和0%。任何癌症后的十年粗生存率为87%，如果第一个癌症是结直肠癌，则为91%，子宫内膜癌为98%，卵巢癌为89%。4个Lynch综合征相关基因的多态性和表达量不同。尽管结肠镜监测，但结直肠癌仍频繁发生，但死亡人数很少。利用我们的数据，已经建立了一个网站http://LScarisk.org，可以计算累积癌症风险，作为林奇综合征遗传咨询的辅助手段。
Estimates of cancer risk and the effects of surveillance in Lynch syndrome have been subject to bias, partly through reliance on retrospective studies. We sought to establish more robust estimates in patients undergoing prospective cancer surveillance. We undertook a multicentre study of patients carrying Lynch syndrome-associated mutations affecting MLH1, MSH2, MSH6 or PMS2. Standardised information on surveillance, cancers and outcomes were collated in an Oracle relational database and analysed by age, sex and mutated gene. 1942 mutation carriers without previous cancer had follow-up including colonoscopic surveillance for 13 782 observation years. 314 patients developed cancer, mostly colorectal (n=151), endometrial (n=72) and ovarian (n=19). Cancers were detected from 25 years onwards in MLH1 and MSH2 mutation carriers, and from about 40 years in MSH6 and PMS2 carriers. Among first cancer detected in each patient the colorectal cancer cumulative incidences at 70 years by gene were 46%, 35%, 20% and 10% for MLH1, MSH2, MSH6 and PMS2 mutation carriers, respectively. The equivalent cumulative incidences for endometrial cancer were 34%, 51%, 49% and 24%; and for ovarian cancer 11%, 15%, 0% and 0%. Ten-year crude survival was 87% after any cancer, 91% if the first cancer was colorectal, 98% if endometrial and 89% if ovarian. The four Lynch syndrome-associated genes had different penetrance and expression. Colorectal cancer occurred frequently despite colonoscopic surveillance but resulted in few deaths. Using our data, a website has been established at http://LScarisk.org enabling calculation of cumulative cancer risks as an aid to genetic counselling in Lynch syndrome.
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影响因子：
168.9
作者：
Burn, John;Gerdes, Anne-Marie;Macrae, Finlay;Mecklin, Jukka-Pekka;Moeslein, Gabriela;Olschwang, Sylviane;Eccles, Diane;Evans, D. Gareth;Maher, Eamonn R.;Bertario, Lucio;Bisgaard, Marie-Luise;Dunlop, Malcolm G.;Ho, Judy W. C.;Hodgson, Shirley V.;Lindblom, Annika;Lubinski, Jan;Morrison, Patrick J.;Murday, Victoria;Ramesar, Raj;Side, Lucy;Scott, Rodney J.;Thomas, Huw J. W.;Vasen, Hans F.;Barker, Gail;Crawford, Gillian;Elliott, Faye;Movahedi, Mohammad;Pylvanainen, Kirsi;Wijnen, Juul T.;Fodde, Riccardo;Lynch, Henry T.;Mathers, John C.;Bishop, D. Timothy
通讯作者：
Bishop, D. Timothy
影响因子：
45.3
作者：
Jenkins, Mark A.;Dowty, James G.;Win, Aung Ko
通讯作者：
Win, Aung Ko
影响因子：
3.6
作者：
Huxley，Nicola;Jones-Hughes，Tracey;Mujica-Mota，Ruben
通讯作者：
Mujica-Mota，Ruben
影响因子：
3.7
作者：
Niskakoski A;Kaur S;Staff S;Renkonen-Sinisalo L;Lassus H;Järvinen HJ;Mecklin JP;Bützow R;Peltomäki P
通讯作者：
Peltomäki P
影响因子：
6.6
作者：
Lynch HT;Casey MJ;Snyder CL;Bewtra C;Lynch JF;Butts M;Godwin AK
通讯作者：
Godwin AK