000148599 001__ 148599 000148599 005__ 20240229105157.0 000148599 0247_ $$2doi$$a10.1200/JCO.2018.78.4777 000148599 0247_ $$2pmid$$apmid:30161022 000148599 0247_ $$2pmc$$apmc:PMC6349460 000148599 0247_ $$2ISSN$$a0732-183X 000148599 0247_ $$2ISSN$$a1527-7755 000148599 0247_ $$2altmetric$$aaltmetric:47533215 000148599 037__ $$aDKFZ-2019-03147 000148599 041__ $$aeng 000148599 082__ $$a610 000148599 1001_ $$aTen Broeke, Sanne W$$b0 000148599 245__ $$aCancer Risks for PMS2-Associated Lynch Syndrome. 000148599 260__ $$aAlexandria, Va.$$bAmerican Society of Clinical Oncology$$c2018 000148599 3367_ $$2DRIVER$$aarticle 000148599 3367_ $$2DataCite$$aOutput Types/Journal article 000148599 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1660201175_9214 000148599 3367_ $$2BibTeX$$aARTICLE 000148599 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000148599 3367_ $$00$$2EndNote$$aJournal Article 000148599 520__ $$aLynch syndrome due to pathogenic variants in the DNA mismatch repair genes MLH1, MSH2, and MSH6 is predominantly associated with colorectal and endometrial cancer, although extracolonic cancers have been described within the Lynch tumor spectrum. However, the age-specific cumulative risk (penetrance) of these cancers is still poorly defined for PMS2-associated Lynch syndrome. Using a large data set from a worldwide collaboration, our aim was to determine accurate penetrance measures of cancers for carriers of heterozygous pathogenic PMS2 variants.A modified segregation analysis was conducted that incorporated both genotyped and nongenotyped relatives, with conditioning for ascertainment to estimates corrected for bias. Hazard ratios (HRs) and corresponding 95% CIs were estimated for each cancer site for mutation carriers compared with the general population, followed by estimation of penetrance.In total, 284 families consisting of 4,878 first- and second-degree family members were included in the analysis. PMS2 mutation carriers were at increased risk for colorectal cancer (cumulative risk to age 80 years of 13% [95% CI, 7.9% to 22%] for males and 12% [95% CI, 6.7% to 21%] for females) and endometrial cancer (13% [95% CI, 7.0%-24%]), compared with the general population (6.6%, 4.7%, and 2.4%, respectively). There was no clear evidence of an increased risk of ovarian, gastric, hepatobiliary, bladder, renal, brain, breast, prostate, or small bowel cancer.Heterozygous PMS2 mutation carriers were at small increased risk for colorectal and endometrial cancer but not for any other Lynch syndrome-associated cancer. This finding justifies that PMS2-specific screening protocols could be restricted to colonoscopies. The role of risk-reducing hysterectomy and bilateral salpingo-oophorectomy for PMS2 mutation carriers needs further discussion. 000148599 536__ $$0G:(DE-HGF)POF3-316$$a316 - Infections and cancer (POF3-316)$$cPOF3-316$$fPOF III$$x0 000148599 588__ $$aDataset connected to CrossRef, PubMed, 000148599 650_7 $$0EC 3.6.1.-$$2NLM Chemicals$$aPMS2 protein, human 000148599 650_7 $$0EC 3.6.1.3$$2NLM Chemicals$$aMismatch Repair Endonuclease PMS2 000148599 7001_ $$avan der Klift, Heleen M$$b1 000148599 7001_ $$aTops, Carli M J$$b2 000148599 7001_ $$aAretz, Stefan$$b3 000148599 7001_ $$aBernstein, Inge$$b4 000148599 7001_ $$aBuchanan, Daniel D$$b5 000148599 7001_ $$ade la Chapelle, Albert$$b6 000148599 7001_ $$aCapella, Gabriel$$b7 000148599 7001_ $$aClendenning, Mark$$b8 000148599 7001_ $$aEngel, Christoph$$b9 000148599 7001_ $$aGallinger, Steven$$b10 000148599 7001_ $$aGomez Garcia, Encarna$$b11 000148599 7001_ $$aFigueiredo, Jane C$$b12 000148599 7001_ $$aHaile, Robert$$b13 000148599 7001_ $$aHampel, Heather L$$b14 000148599 7001_ $$aHopper, John L$$b15 000148599 7001_ $$aHoogerbrugge, Nicoline$$b16 000148599 7001_ $$0P:(DE-He78)11747cd1dc061b9333c0e3a3ff31bf2f$$avon Knebel Doeberitz, Magnus$$b17$$udkfz 000148599 7001_ $$aLe Marchand, Loic$$b18 000148599 7001_ $$aLetteboer, Tom G W$$b19 000148599 7001_ $$aJenkins, Mark A$$b20 000148599 7001_ $$aLindblom, Annika$$b21 000148599 7001_ $$aLindor, Noralane M$$b22 000148599 7001_ $$aMensenkamp, Arjen R$$b23 000148599 7001_ $$aMøller, Pål$$b24 000148599 7001_ $$aNewcomb, Polly A$$b25 000148599 7001_ $$avan Os, Theo A M$$b26 000148599 7001_ $$aPearlman, Rachel$$b27 000148599 7001_ $$aPineda, Marta$$b28 000148599 7001_ $$aRahner, Nils$$b29 000148599 7001_ $$aRedeker, Egbert J W$$b30 000148599 7001_ $$aOlderode-Berends, Maran J W$$b31 000148599 7001_ $$aRosty, Christophe$$b32 000148599 7001_ $$aSchackert, Hans K$$b33 000148599 7001_ $$aScott, Rodney$$b34 000148599 7001_ $$aSenter, Leigha$$b35 000148599 7001_ $$aSpruijt, Liesbeth$$b36 000148599 7001_ $$aSteinke-Lange, Verena$$b37 000148599 7001_ $$aSuerink, Manon$$b38 000148599 7001_ $$aThibodeau, Stephen$$b39 000148599 7001_ $$aVos, Yvonne J$$b40 000148599 7001_ $$aWagner, Anja$$b41 000148599 7001_ $$aWinship, Ingrid$$b42 000148599 7001_ $$aHes, Frederik J$$b43 000148599 7001_ $$aVasen, Hans F A$$b44 000148599 7001_ $$aWijnen, Juul T$$b45 000148599 7001_ $$aNielsen, Maartje$$b46 000148599 7001_ $$aWin, Aung Ko$$b47 000148599 773__ $$0PERI:(DE-600)2005181-5$$a10.1200/JCO.2018.78.4777$$gVol. 36, no. 29, p. 2961 - 2968$$n29$$p2961 - 2968$$tJournal of clinical oncology$$v36$$x1527-7755$$y2018 000148599 909CO $$ooai:inrepo02.dkfz.de:148599$$pVDB 000148599 9101_ $$0I:(DE-588b)2036810-0$$6P:(DE-He78)11747cd1dc061b9333c0e3a3ff31bf2f$$aDeutsches Krebsforschungszentrum$$b17$$kDKFZ 000148599 9131_ $$0G:(DE-HGF)POF3-316$$1G:(DE-HGF)POF3-310$$2G:(DE-HGF)POF3-300$$3G:(DE-HGF)POF3$$4G:(DE-HGF)POF$$aDE-HGF$$bGesundheit$$lKrebsforschung$$vInfections and cancer$$x0 000148599 9141_ $$y2018 000148599 915__ $$0StatID:(DE-HGF)0420$$2StatID$$aNationallizenz 000148599 915__ $$0StatID:(DE-HGF)0100$$2StatID$$aJCR$$bJ CLIN ONCOL : 2017 000148599 915__ $$0StatID:(DE-HGF)0200$$2StatID$$aDBCoverage$$bSCOPUS 000148599 915__ $$0StatID:(DE-HGF)0300$$2StatID$$aDBCoverage$$bMedline 000148599 915__ $$0StatID:(DE-HGF)0310$$2StatID$$aDBCoverage$$bNCBI Molecular Biology Database 000148599 915__ $$0StatID:(DE-HGF)0320$$2StatID$$aDBCoverage$$bPubMed Central 000148599 915__ $$0StatID:(DE-HGF)0199$$2StatID$$aDBCoverage$$bClarivate Analytics Master Journal List 000148599 915__ $$0StatID:(DE-HGF)0110$$2StatID$$aWoS$$bScience Citation Index 000148599 915__ $$0StatID:(DE-HGF)0150$$2StatID$$aDBCoverage$$bWeb of Science Core Collection 000148599 915__ $$0StatID:(DE-HGF)0111$$2StatID$$aWoS$$bScience Citation Index Expanded 000148599 915__ $$0StatID:(DE-HGF)1110$$2StatID$$aDBCoverage$$bCurrent Contents - Clinical Medicine 000148599 915__ $$0StatID:(DE-HGF)1030$$2StatID$$aDBCoverage$$bCurrent Contents - Life Sciences 000148599 915__ $$0StatID:(DE-HGF)9925$$2StatID$$aIF >= 25$$bJ CLIN ONCOL : 2017 000148599 9201_ $$0I:(DE-He78)G105-20160331$$kG105$$lGentherapie von Tumoren$$x0 000148599 980__ $$ajournal 000148599 980__ $$aVDB 000148599 980__ $$aI:(DE-He78)G105-20160331 000148599 980__ $$aUNRESTRICTED