One to 2-year surveillance intervals reduce risk of colorectal cancer in families with Lynch syndrome.
OBJECTIVE
Two percent to 4% of all cases of colorectal cancer (CRC) are associated with Lynch syndrome. Dominant clustering of CRC (non-Lynch syndrome) accounts for 1%-3% of the cases. Because carcinogenesis is accelerated in Lynch syndrome, an intensive colonoscopic surveillance program has been recommended since 1995. The aim of the study was to evaluate the effectiveness of this program.


METHODS
The study included 205 Lynch syndrome families with identified mutations in one of the mismatch repair genes (745 mutation carriers). We also analyzed data from non-Lynch syndrome families (46 families, 344 relatives). Patients were observed from January 1, 1995, until January 1, 2009. End points of the study were CRC or date of the last colonoscopy.


RESULTS
After a mean follow-up of 7.2 years, 33 patients developed CRC under surveillance. The cumulative risk of CRC was 6% after the 10-year follow-up period. The risk of CRC was higher in carriers older than 40 years and in carriers of MLH1 and MSH2 mutations. After a mean follow-up of 7.0 years, 6 cases of CRC were detected among non-Lynch syndrome families. The risk of CRC was significantly higher among families with Lynch syndrome, compared with those without.


CONCLUSIONS
With surveillance intervals of 1-2 years, members of families with Lynch syndrome have a lower risk of developing CRC than with surveillance intervals of 2-3 years. Because of the low risk of CRC in non-Lynch syndrome families, a less intensive surveillance protocol can be recommended.
Vasen
Hans F A
HF
The Netherlands Foundation for the Detection of Hereditary Tumours, Leiden, The Netherlands. hfavasen@stoet.nl
Abdirahman
Mohamed
M
Brohet
Richard
R
Langers
Alexandra M J
AM
Kleibeuker
Jan H
JH
van Kouwen
Mariette
M
Koornstra
Jan Jacob
JJ
Boot
Henk
H
Cats
Annemieke
A
Dekker
Evelien
E
Sanduleanu
Silvia
S
Poley
Jan-Werner
JW
Hardwick
James C H
JC
de Vos Tot Nederveen Cappel
Wouter H
WH
van der Meulen-de Jong
Andrea E
AE
Tan
T Gie
TG
Jacobs
Maarten A J M
MA
Mohamed
Faig Lall A
FL
de Boer
Sijbrand Y
SY
van de Meeberg
Paul C
PC
Verhulst
Marie-Louise
ML
Salemans
Jan M
JM
van Bentem
Nico
N
Westerveld
B Dik
BD
Vecht
Juda
J
Nagengast
Fokko M
FM
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics / Q000517:prevention & control*; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000235:genetics*; D053843:DNA Mismatch Repair / Q000235:genetics; D005190:Family; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein / Q000235:genetics; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics; D012306:Risk; D013997:Time Factors
D048868:Adaptor Proteins, Signal Transducing; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C497172:MSH2 protein, human; D000070957:MutL Protein Homolog 1; D051718:MutS Homolog 2 Protein