Imperial College London
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DrKevinMonahan

Faculty of Medicine, Department of Surgery & Cancer

Honorary Clinical Senior Lecturer
 
 
 
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k.monahan Website

 
 
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CRUKSt Marks HospitalNorthwick Park and St Marks Site

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Summary

 

Publications

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BibTex format

@article{Win:2021:10.1016/s1470-2045(21)00189-3,
author = {Win, AK and Dowty, JG and Reece, JC and Lee, G and Templeton, AS and Plazzer, J-P and Buchanan, DD and Akagi, K and Aksoy, S and Alonso, A and Alvarez, K and Amor, DJ and Ankathil, R and Aretz, S and Arnold, JL and Aronson, M and Austin, R and Backman, A-S and Bajwa-ten, Broeke SW and Barca-Tierno, V and Barwell, J and Bernstein, I and Berthet, P and Betz, B and Bignon, Y-J and Boisjoli, T and Bonadona, V and Briollais, L and Brunet, J and Bucksch, K and Buecher, B and Buettner, R and Burn, J and Caldés, T and Capella, G and Caron, O and Casey, G and Chew, MH and Choi, Y-H and Church, J and Clendenning, M and Colas, C and Cops, EJ and Coupier, I and Cruz-Correa, M and de, la Chapelle A and de, Wind N and Dbniak, T and Della, Valle A and Delnatte, C and Dhooge, M and Dominguez-Valentin, M and Drouet, Y and Duijkers, FA and Engel, C and Esperon, P and Evans, DG and Falcón, de Vargas A and Figueiredo, JC and Foulkes, W and Fourme, E and Frebourg, T and Gallinger, S and Garre, P and Genuar},
doi = {10.1016/s1470-2045(21)00189-3},
journal = {The Lancet Oncology},
title = {Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study},
url = {http://dx.doi.org/10.1016/s1470-2045(21)00189-3},
year = {2021}
}
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TY  - JOUR
AB  - BackgroundExisting clinical practice guidelines for carriers of pathogenic variants of DNA mismatch repair genes (Lynch syndrome) are based on the mean age-specific cumulative risk (penetrance) of colorectal cancer for all carriers of pathogenic variants in the same gene. We aimed to estimate the variation in the penetrance of colorectal cancer between carriers of pathogenic variants in the same gene by sex and continent of residence.MethodsIn this retrospective cohort study, we sourced data from the International Mismatch Repair Consortium, which comprises 273 members from 122 research centres or clinics in 32 countries from six continents who are involved in Lynch syndrome research. Families with at least three members and at least one confirmed carrier of a pathogenic or likely pathogenic variant in a DNA mismatch repair gene (MLH1, MSH2, MSH6, or PMS2) were included. The families of probands with known de-novo pathogenic variants were excluded. Data were collected on the method of ascertainment of the family, sex, carrier status, cancer diagnoses, and ages at the time of pedigree collection and at last contact or death. We used a segregation analysis conditioned on ascertainment to estimate the mean penetrance of colorectal cancer and modelled unmeasured polygenic factors to estimate the variation in penetrance. The existence of unknown familial risk factors modifying colorectal cancer risk for Lynch syndrome carriers was tested by use of a Wald p value for the null hypothesis that the polygenic SD is zero.Findings5585 families with Lynch syndrome from 22 countries were eligible for the analysis. Of these, there were insufficient numbers to estimate penetrance for Asia and South America, and for those with EPCAM variants. Therefore, we used data (collected between July 11, 2014, and Dec 31, 2018) from 5255 families (1829 MLH1, 2179 MSH2, 798 MSH6, and 449 PMS2), comprising 79 809 relatives, recruited in 15 countries in North America, Europe, and Australas
AU  - Win,AK
AU  - Dowty,JG
AU  - Reece,JC
AU  - Lee,G
AU  - Templeton,AS
AU  - Plazzer,J-P
AU  - Buchanan,DD
AU  - Akagi,K
AU  - Aksoy,S
AU  - Alonso,A
AU  - Alvarez,K
AU  - Amor,DJ
AU  - Ankathil,R
AU  - Aretz,S
AU  - Arnold,JL
AU  - Aronson,M
AU  - Austin,R
AU  - Backman,A-S
AU  - Bajwa-ten,Broeke SW
AU  - Barca-Tierno,V
AU  - Barwell,J
AU  - Bernstein,I
AU  - Berthet,P
AU  - Betz,B
AU  - Bignon,Y-J
AU  - Boisjoli,T
AU  - Bonadona,V
AU  - Briollais,L
AU  - Brunet,J
AU  - Bucksch,K
AU  - Buecher,B
AU  - Buettner,R
AU  - Burn,J
AU  - Caldés,T
AU  - Capella,G
AU  - Caron,O
AU  - Casey,G
AU  - Chew,MH
AU  - Choi,Y-H
AU  - Church,J
AU  - Clendenning,M
AU  - Colas,C
AU  - Cops,EJ
AU  - Coupier,I
AU  - Cruz-Correa,M
AU  - de,la Chapelle A
AU  - de,Wind N
AU  - Dbniak,T
AU  - Della,Valle A
AU  - Delnatte,C
AU  - Dhooge,M
AU  - Dominguez-Valentin,M
AU  - Drouet,Y
AU  - Duijkers,FA
AU  - Engel,C
AU  - Esperon,P
AU  - Evans,DG
AU  - Falcón,de Vargas A
AU  - Figueiredo,JC
AU  - Foulkes,W
AU  - Fourme,E
AU  - Frebourg,T
AU  - Gallinger,S
AU  - Garre,P
AU  - Genuardi,M
AU  - Gerdes,A-M
AU  - Gima,LM
AU  - Giraud,S
AU  - Goodwin,A
AU  - Görgens,H
AU  - Green,K
AU  - Guillem,J
AU  - Guillén-Ponce,C
AU  - Guimbaud,R
AU  - Guindalini,RSC
AU  - Half,EE
AU  - Hall,MJ
AU  - Hampel,H
AU  - Hansen,TVO
AU  - Heinimann,K
AU  - Hes,FJ
AU  - Hill,J
AU  - Ho,JWC
AU  - Holinski-Feder,E
AU  - Hoogerbrugge,N
AU  - Hüneburg,R
AU  - Huntley,V
AU  - James,PA
AU  - Jensen,UB
AU  - John,T
AU  - Juhari,WKW
AU  - Kalady,M
AU  - Kastrinos,F
AU  - Kloor,M
AU  - Kohonen-Corish,MRJ
AU  - Krogh,LN
AU  - Kupfer,SS
AU  - Ladabaum,U
AU  - Lagerstedt-Robinson,K
AU  - Lalloo,F
AU  - Lasset,C
AU  - Latchford,A
AU  - Laurent-Puig,P
AU  - Lautrup,CK
AU  - Leggett,BA
AU  - Lejeune,S
AU  - LeMarchand,L
AU  - Ligtenberg,M
AU  - Lindor,N
AU  - Loeffler,M
AU  - Longy,M
AU  - Lopez,F
AU  - Lowery,J
AU  - Lubiski,J
AU  - Lucassen,AM
AU  - Lynch,PM
AU  - Maliska,K
AU  - Matsubara,N
AU  - Mecklin,J-P
AU  - Møller,P
AU  - Monahan,K
AU  - Morrison,PJ
AU  - Nattermann,J
AU  - Navarro,M
AU  - Neffa,F
AU  - Neklason,D
AU  - Newcomb,PA
AU  - Ngeow,J
AU  - Nichols,C
AU  - Nielsen,M
AU  - Nixon,DM
AU  - Nogues,C
AU  - Okkels,H
AU  - Olschwang,S
AU  - Pachter,N
AU  - Pai,RK
AU  - Palmero,EI
AU  - Pande,M
AU  - Parry,S
AU  - Patel,SG
AU  - Pearlman,R
AU  - Perne,C
AU  - Pineda,M
AU  - Poplawski,NK
AU  - Pylvänäinen,K
AU  - Qiu,J
AU  - Rahner,N
AU  - Ramesar,R
AU  - Rasmussen,LJ
AU  - Redler,S
AU  - Reis,RM
AU  - Ricciardiello,L
AU  - Rogoa-Janiszewska,E
AU  - Rosty,C
AU  - Samadder,NJ
AU  - Sampson,JR
AU  - Schackert,HK
AU  - Schmiegel,W
AU  - Schulmann,K
AU  - Schuster,H
AU  - Scott,R
AU  - Senter,L
AU  - Seppälä,TT
AU  - Shtoyerman,R
AU  - Sijmons,RH
AU  - Snyder,C
AU  - Solomon,IB
AU  - Soto,JL
AU  - Southey,MC
AU  - Spigelman,A
AU  - Spirandelli,F
AU  - Spurdle,AB
AU  - St
DO  - 10.1016/s1470-2045(21)00189-3
PY  - 2021///
SN  - 1470-2045
TI  - Variation in the risk of colorectal cancer in families with Lynch syndrome: a retrospective cohort study
T2  - The Lancet Oncology
UR  - http://dx.doi.org/10.1016/s1470-2045(21)00189-3
UR  - https://www.sciencedirect.com/science/article/pii/S1470204521001893?via%3Dihub
ER  -
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