Lynch Syndrome Caused by Germline PMS2 Mutations: Delineating the Cancer Risk

被引：155

作者：

ten Broeke, Sanne W. ^{[1
]}

Brohet, Richard M. ^{[3
]}

Tops, Carli M. ^{[1
]}

van der Klift, Heleen M. ^{[1
]}

Velthuizen, Mary E. ^{[4
]}

Bernstein, Inge ^{[11
,12
]}

Capella Munar, Gabriel ^{[13
]}

Garcia, Encarna Gomez ^{[5
]}

Hoogerbrugge, Nicoline ^{[6
]}

Letteboer, Tom G. W. ^{[4
]}

Menko, Fred H. ^{[7
]}

Lindblom, Annika ^{[14
]}

Mensenkamp, Arjen R. ^{[6
]}

Moller, Pal ^{[15
]}

Van Os, Theo A. ^{[8
]}

Rahner, Nils ^{[16
]}

Redeker, Bert J. W. ^{[8
]}

Sijmons, Rolf H. ^{[9
]}

Spruijt, Liesbeth ^{[6
]}

Suerink, Manon ^{[1
]}

Vos, Yvonne J. ^{[9
]}

Wagner, Anja ^{[10
]}

Hes, Frederik J. ^{[1
]}

Vasen, Hans F. ^{[1
,2
]}

Nielsen, Maartje ^{[1
]}

Wijnen, Juul T. ^{[1
]}

机构：

[1] Leiden Univ, Med Ctr, Leiden, Netherlands

[2] Netherlands Fdn Detect Hereditary Tumors, Leiden, Netherlands

[3] Spaarne Hosp, Res Ctr Linnaeus Inst, Hoofddorp, Netherlands

[4] Univ Med Ctr Utrecht, Utrecht, Netherlands

[5] Maastricht Univ, Med Ctr, NL-6200 MD Maastricht, Netherlands

[6] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands

[7] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands

[8] Univ Amsterdam, Acad Med Ctr, NL-1105 AZ Amsterdam, Netherlands

[9] Univ Groningen, Univ Med Ctr Groningen, Groningen, Netherlands

[10] Erasmus Univ, Med Ctr, Rotterdam, Netherlands

[11] Aalborg Univ Hosp, Aalborg, Denmark

[12] Hvidovre Univ Hosp Copenhagen, Danish Hereditary Nonpolyposis Colorectal Canc Re, Copenhagen, Denmark

[13] Inst Invest Biomed Bellvitge, Catalan Inst Oncol, Hereditary Canc Program, Lhospitalet De Llobregat, Spain

[14] Karolinska Univ Hosp, Karolinska Inst, Solna, Sweden

[15] Oslo Univ Hosp, Res Grp Inherited Canc, Oslo, Norway

[16] Univ Dusseldorf, Inst Human Genet, Dusseldorf, Germany

来源：

JOURNAL OF CLINICAL ONCOLOGY | 2015年 / 33卷 / 04期

关键词：

NONPOLYPOSIS COLORECTAL-CANCER; CLINICAL MANAGEMENT; COLON-CANCER; CARRIERS; SURVEILLANCE; GUIDELINES; VARIANTS; FAMILIES; MLH1; CRITERIA;

D O I：

10.1200/JCO.2014.57.8088

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose The clinical consequences of PMS2 germline mutations are poorly understood compared with other Lynch-associated mismatch repair gene (MMR) mutations. The aim of this European cohort study was to define the cancer risk faced by PMS2 mutation carriers. Methods Data were collected from 98 PMS2 families ascertained from family cancer clinics that included a total of 2,548 family members and 377 proven mutation carriers. To adjust for potential ascertainment bias, a modified segregation analysis model was used to calculate colorectal cancer (CRC) and endometrial cancer (EC) risks. Standardized incidence ratios (SIRs) were calculated to estimate risks for other Lynch syndrome-associated cancers. Results The cumulative risk (CR) of CRC for male mutation carriers by age 70 years was 19%. The CR among female carriers was 11% for CRC and 12% for EC. The mean age of CRC development was 52 years, and there was a significant difference in mean age of CRC between the probands (mean, 47 years; range, 26 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P < .001). Significant SIRs were observed for cancers of the small bowel, ovaries, breast, and renal pelvis. Conclusion CRC and EC risks were found to be markedly lower than those previously reported for the other MMR. However, these risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a substantial variation in cancer phenotype within and between families, suggesting the influence of genetic modifiers and lifestyle factors on cancer risks. (C) 2014 by American Society of Clinical Oncology

引用

页码：319 / U172

页数：10

共 39 条

[1] A weighted cohort approach for analysing factors modifying disease risks in carriers of high-risk susceptibility genes [J].

Antoniou, AC ;

Goldgar, DE ;

Andrieu, N ;

Chang-Claude, J ;

Brohet, R ;

Rookus, MA ;

Easton, DF .

GENETIC EPIDEMIOLOGY, 2005, 29 (01) :1-11

[2] Risks of Lynch Syndrome Cancers for MSH6 Mutation Carriers [J].

Baglietto, Laura ;

Lindor, Noralane M. ;

Dowty, James G. ;

White, Darren M. ;

Wagner, Anja ;

Garcia, Encarna B. Gomez ;

Vriends, Annette H. J. T. ;

Cartwright, Nicola R. ;

Barnetson, Rebecca A. ;

Farrington, Susan M. ;

Tenesa, Albert ;

Hampel, Heather ;

Buchanan, Daniel ;

Arnold, Sven ;

Young, Joanne ;

Walsh, Michael D. ;

Jass, Jeremy ;

Macrae, Finlay ;

Antill, Yoland ;

Winship, Ingrid M. ;

Giles, Graham G. ;

Goldblatt, Jack ;

Parry, Susan ;

Suthers, Graeme ;

Leggett, Barbara ;

Butz, Malinda ;

Aronson, Melyssa ;

Poynter, Jenny N. ;

Baron, John A. ;

Le Marchand, Loic ;

Haile, Robert ;

Gallinger, Steve ;

Hopper, John L. ;

Potter, John ;

de la Chapelle, Albert ;

Vasen, Hans F. ;

Dunlop, Malcolm G. ;

Thibodeau, Stephen N. ;

Jenkins, Mark A. .

JNCI-JOURNAL OF THE NATIONAL CANCER INSTITUTE, 2010, 102 (03) :193-201

[3] Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: Report from the constitutional mismatch repair deficiency consortium [J].

Bakry, Doua ;

Aronson, Melyssa ;

Durno, Carol ;

Rimawi, Hala ;

Farah, Roula ;

Alharbi, Qasim Kholaif ;

Alharbi, Musa ;

Shamvil, Ashraf ;

Ben-Shachar, Shay ;

Mistry, Matthew ;

Constantini, Shlomi ;

Dvir, Rina ;

Qaddoumi, Ibrahim ;

Gallinger, Steven ;

Lerner-Ellis, Jordan ;

Pollett, Aaron ;

Stephens, Derek ;

Kelies, Steve ;

Chao, Elizabeth ;

Malkin, David ;

Bouffet, Eric ;

Hawkins, Cynthia ;

Tabori, Uri .

EUROPEAN JOURNAL OF CANCER, 2014, 50 (05) :987-996

[4] Cancer risk in Lynch Syndrome [J].

Barrow, Emma ;

Hill, James ;

Evans, D. Gareth .

FAMILIAL CANCER, 2013, 12 (02) :229-240

[5] Surveillance for urinary tract cancer in Lynch syndrome [J].

Bernstein, Inge Thomsen ;

Myrhoj, Torben .

FAMILIAL CANCER, 2013, 12 (02) :279-284

[6] Cancer Risks Associated With Germline Mutations in MLH1, MSH2, and MSH6 Genes in Lynch Syndrome [J].

Bonadona, Valerie ;

Bonaiti, Bernard ;

Olschwang, Sylviane ;

Grandjouan, Sophie ;

Huiart, Laetitia ;

Longy, Michel ;

Guimbaud, Rosine ;

Buecher, Bruno ;

Bignon, Yves-Jean ;

Caron, Olivier ;

Colas, Chrystelle ;

Nogues, Catherine ;

Lejeune-Dumoulin, Sophie ;

Olivier-Faivre, Laurence ;

Polycarpe-Osaer, Florence ;

Nguyen, Tan Dat ;

Desseigne, Francoise ;

Saurin, Jean-Christophe ;

Berthet, Pascaline ;

Leroux, Dominique ;

Duffour, Jacqueline ;

Manouvrier, Sylvie ;

Frebourg, Thierry ;

Sobol, Hagay ;

Lasset, Christine ;

Bonaiti-Pellie, Catherine .

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 2011, 305 (22) :2304-2310

[7] Incidental copy-number variants identified by routine genome testing in a clinical population [J].

Boone, Philip M. ;

Soens, Zachry T. ;

Campbell, Ian M. ;

Stankiewicz, Pawel ;

Cheung, Sau Wai ;

Patel, Ankita ;

Beaudet, Arthur L. ;

Plon, Sharon E. ;

Shaw, Chad A. ;

McGuire, Amy L. ;

Lupski, James R. .

GENETICS IN MEDICINE, 2013, 15 (01) :45-54

[8] Refining the role of pms2 in Lynch syndrome: germline mutational analysis improved by comprehensive assessment of variants [J].

Borras, Ester ;

Pineda, Marta ;

Cadinanos, Juan ;

del Valle, Jesus ;

Brieger, Angela ;

Hinrichsen, Inga ;

Cabanillas, Ruben ;

Navarro, Matilde ;

Brunet, Joan ;

Sanjuan, Xavier ;

Musulen, Eva ;

van der Klift, Helen ;

Lazaro, Conxi ;

Plotz, Guido ;

Blanco, Ignacio ;

Capella, Gabriel .

JOURNAL OF MEDICAL GENETICS, 2013, 50 (08) :552-563

[9] Breast and ovarian cancer risks in a large series of clinically ascertained families with a high proportion of BRCA1 and BRCA2 Dutch founder mutations [J].

Brohet, Richard M. ;

Velthuizen, Maria E. ;

Hogervorst, Frans B. L. ;

Meijers-Heijboer, Hanne E. J. ;

Seynaeve, Caroline ;

Collee, Margriet J. ;

Verhoef, Senno ;

Ausems, Margreet G. E. M. ;

Hoogerbrugge, Nicoline ;

van Asperen, Christi J. ;

Garcia, Encarna Gomez ;

Menko, Fred ;

Oosterwijk, Jan C. ;

Devilee, Peter ;

van't Veer, Laura J. ;

van Leeuwen, Flora E. ;

Easton, Douglas F. ;

Rookus, Matti A. ;

Antoniou, Antonis C. .

JOURNAL OF MEDICAL GENETICS, 2014, 51 (02) :98-107

[10]

Castera L., 2014, Eur J Hum Genet

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