Rapid development of colorectal neoplasia in patients with Lynch syndrome.
OBJECTIVE
Patients with Lynch syndrome have a high risk for colorectal adenomas and carcinomas. We evaluated the development of colorectal neoplasia in these patients.


METHODS
We assessed serial colonoscopy findings from 54 persons from 29 pedigrees with pathogenic mutations in MSH2 or MLH1; we evaluated the development of colorectal neoplasia by age, sex, tumor location, and number (mean follow-up time, 9.3 years; colonoscopy interval, 1.7 ± 1.2 years; 112 adenomas and 31 cancers). Differences in colorectal phenotype were analyzed by genotype, and dwell time was calculated for advanced neoplasias.


RESULTS
Among mutation carriers, the cumulative risk of colorectal neoplasia was 43% by age 40 years and 72% by 80 years. There were no statistically significant associations between time to development of colorectal neoplasia and sex or mutation type. Most female patients had left-sided neoplasms, whereas most male patients developed right-sided lesions. The mean cumulative numbers of neoplastic lesions in patients were 1.3 ± 0.5 by age 30 years and 7.6 ± 6.8 by age 80 years. Polyp dwell time was 33.0 ± 16.2 months and 35.2 ± 22.3 months for advanced adenoma and colorectal cancer, respectively. The 5-year survival rate for patients with colorectal cancer was 96%.


CONCLUSIONS
High percentages of individuals with pathogenic mutations in MSH2 or MLH1 develop colorectal neoplasia by age 40. Left-sided colorectal neoplasias are more frequent in female patients. The development of 3 or more colorectal neoplasms by age 30 years indicates a possible polyposis syndrome rather than Lynch syndrome. Polyp dwell time is short for advanced neoplasias, arguing for annual colonoscopic screening and surveillance.
Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Daniel L
DL
Edelstein
Jennifer
J
Axilbund
Melanie
M
Baxter
Linda M
LM
Hylind
Katharine
K
Romans
Constance A
CA
Griffin
Marcia
M
Cruz-Correa
Francis M
FM
Giardiello
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D003106:Colon / Q000473:pathology*; D003113:Colonoscopy; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000473:pathology*; 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; D055815:Young Adult
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