Cancer risk and survival in path_MMR carriers by gene and gender up to 75 years of age: a report from the Prospective Lynch Syndrome Database

被引：428

作者：

Moller, Pal ^{[1
,2
,3
]}

Seppala, Toni T. ^{[4
]}

Bernstein, Inge ^{[5
,6
]}

Holinski-Feder, Elke ^{[7
,8
]}

Sala, Paulo ^{[9
]}

Evans, D. Gareth ^{[10
,11
]}

Lindblom, Annika ^{[12
]}

Macrae, Finlay ^{[13
,14
]}

Blanco, Ignacio ^{[15
]}

Sijmons, Rolf H. ^{[16
]}

Jeffries, Jacqueline ^{[17
]}

Vasen, Hans F. A. ^{[18
]}

Burn, John ^{[19
]}

Nakken, Sigve ^{[2
]}

Hovig, Eivind ^{[2
,20
,21
]}

Rodland, Einar Andreas ^{[2
]}

Tharmaratnam, Kukatharmini ^{[22
]}

Cappel, Wouter H. de Vos Tot Nederveen ^{[23
]}

Hill, James ^{[24
,25
]}

Wijnen, Juul T. ^{[26
,27
]}

Jenkins, Mark A. ^{[28
]}

Green, Kate ^{[10
,11
]}

Lalloo, Fiona ^{[10
,11
]}

Sunde, Lone ^{[6
,29
,30
]}

Mints, Miriam ^{[31
]}

Bertario, Lucio ^{[9
]}

Pineda, Marta ^{[15
]}

Navarro, Matilde ^{[15
]}

Morak, Monika ^{[7
,8
]}

Renkonen-Sinisalo, Laura ^{[4
,32
]}

Valentin, Mev Dominguez ^{[1
,2
]}

Frayling, Ian M.

Plazzer, John-Paul ^{[13
]}

Pylvanainen, Kirsi ^{[33
]}

Genuardi, Maurizio ^{[34
]}

Mecklin, Jukka-Pekka ^{[35
]}

Moeslein, Gabriela

Sampson, Julian R. ^{[17
]}

Capella, Gabriel ^{[15
,36
]}

机构：

[1] Oslo Univ Hosp, Norwegian Radium Hosp, Dept Med Genet, Oslo, Norway

[2] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Res, Dept Tumor Biol, Oslo, Norway

[3] Univ Witten Herdecke, HELIOS Klinikum Wuppertal, Ctr Hereditary Tumors, Wuppertal, Germany

[4] Univ Helsinki, Helsinki Univ Cent Hosp, Dept Gastrointestinal Surg, Helsinki, Finland

[5] Copenhagen Univ Hosp, Clin Res Ctr, Danish Hereditary Nonpolyposis Colorectal Canc Re, Hvidovre, Denmark

[6] Aalborg Univ Hosp, Dept Surg Gastroenterol, Aalborg, Denmark

[7] Klinikum Univ Munchen, Med Klin & Poliklin 4, Campus Innenstadt, Ziemssenstr, Germany

[8] MGZ Med Genet Zentrum, Munich, Germany

[9] IRCCS Ist Nazl Tumori Milan, Unit Hereditary Digest Tract Tumors, Milan, Italy

[10] Cent Manchester Univ Hosp NHS Fdn Trust, Manchester Ctr Genom Med, London, England

[11] Univ Manchester, Manchester Ctr Genom Med, London, England

[12] Karolinska Inst, Dept Mol Med & Surg, Stockholm, Sweden

[13] Royal Melbourne Hosp, Colorectal Med & Genet, Melborne, Australia

[14] Univ Melbourne, Dept Med, Melbourne, Vic, Australia

[15] IDIBELL, Inst Catala Oncol, Hereditary Canc Program, Barcelona, Spain

[16] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[17] Cardiff Univ, Sch Med, Inst Med Genet, Div Canc & Genet, Hth Pk, Cardiff, S Glam, Wales

[18] Leiden Univ, Med Ctr, Dept Gastroenterol & Hepatol, Leiden, Netherlands

[19] Newcastle Univ, Inst Genet Med, Newcastle Upon Tyne, Tyne & Wear, England

[20] Oslo Univ Hosp, Norwegian Radium Hosp, Inst Canc Genet & Informat, Oslo, Norway

[21] Univ Oslo, Dept Informat, Oslo, Norway

[22] Univ Lancaster, Dept Math & Stat, Lancaster, England

[23] Isala Clin, Dept Gastroenterol & Hepatol, Zwolle, Netherlands

[24] Cent Manchester Univ Hosp NHS Fdn Trust, Dept Surg, London, England

[25] Univ Manchester, London, England

[26] Univ Med Ctr, Dept Clin Genet, Leiden, Netherlands

[27] Univ Med Ctr, Dept Human Genet Leiden, Leiden, Netherlands

[28] Univ Melbourne, Melbourne Sch Populat & Global Hlth, Ctr Epidemiol & Biostat, Parkville, Vic, Australia

[29] Aarhus Univ Hosp, Dept Clin Genet, Aarhus, Denmark

[30] Aarhus Univ, Dept Biomed, Aarhus, Denmark

[31] Karolinska Inst, Karolinska Univ Hosp, Div Obstet & Gyneacol, Dept Womens & Childrens Hlth, Stockholm, Sweden

[32] Univ Helsinki, Genome Scale Biol Res Program, Helsinki, Finland

[33] Cent Finland Hlth Care Dist, Dept Educ & Sci, Yvaskyla, Finland

[34] Univ Cattolica Sacro Cuore, A Gemelli Fac Med, Inst Genom Med, Rome, Italy

[35] Univ Eastern Finland, Kuopio, Finland

[36] Univ Witten Herdecke, HELIOS Klinikum Wuppertal, Ctr Hereditary Tumors, Wuppertal, Germany

来源：

GUT | 2018年 / 67卷 / 07期

基金：

英国医学研究理事会; 瑞典研究理事会;

关键词：

MUTATION CARRIERS; BREAST-CANCER; GUIDELINES; MANAGEMENT;

D O I：

10.1136/gutjnl-2017-314057

中图分类号：

R57 [消化系及腹部疾病];

学科分类号：

摘要：

Background Most patients with path_MMR gene variants (Lynch syndrome (LS)) now survive both their first and subsequent cancers, resulting in a growing number of older patients with LS for whom limited information exists with respect to cancer risk and survival. Objective and design This observational, international, multicentre study aimed to determine prospectively observed incidences of cancers and survival in path_MMR carriers up to 75 years of age. Results 3119 patients were followed for a total of 24 475 years. Cumulative incidences at 75 years (risks) for colorectal cancer were 46%, 43% and 15% in path_MLH1, path_MSH2 and path_MSH6 carriers; for endometrial cancer 43%, 57% and 46%; for ovarian cancer 10%, 17% and 13%; for upper gastrointestinal (gastric, duodenal, bile duct or pancreatic) cancers 21%, 10% and 7%; for urinary tract cancers 8%, 25% and 11%; for prostate cancer 17%, 32% and 18%; and for brain tumours 1%, 5% and 1%, respectively. Ovarian cancer occurred mainly premenopausally. By contrast, upper gastrointestinal, urinary tract and prostate cancers occurred predominantly at older ages. Overall 5-year survival for prostate cancer was 100%, urinary bladder 93%, ureter 85%, duodenum 67%, stomach 61%, bile duct 29%, brain 22% and pancreas 0%. Path_PMS2 carriers had lower risk for cancer. Conclusion C arriers of different path_MMR variants exhibit distinct patterns of cancer risk and survival as they age. Risk estimates for counselling and planning of surveillance and treatment should be tailored to each patient's age, gender and path_MMR variant. We have updated our open-access website www. lscarisk. org to facilitate this.

引用

页码：1306 / 1316

页数：11

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