Original article—alimentary tract
Rapid Development of Colorectal Neoplasia in Patients With Lynch Syndrome

https://doi.org/10.1016/j.cgh.2010.10.033Get rights and content

Background & Aims

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.

Section snippets

Study Population

Patients with LS in the Johns Hopkins Hereditary Colorectal Cancer Registry were included in this study. All patients had a deleterious germline mutation in either the MLH1 or MSH2 mismatch repair genes and had undergone at least 1 colonoscopic surveillance procedure. All the patients enrolled in the study were unaffected with colorectal cancer or LS-associated cancers before their first colonoscopy. This study was approved by the Johns Hopkins Joint Committee on Clinical Investigation

Results

In total, 54 mismatch repair mutation positive patients from 29 pedigrees had 1 or more colonoscopic evaluations (Table 1). These patients underwent a total of 282 colonoscopies (Table 2). The mean age at first colonoscopy was 39.5 ± 10.8 years and at last colonoscopy was 48.8 ± 12.9 years. The mean colonoscopic follow-up was 9.3 years, and the mean interval between colonoscopies in this patient group was 1.7 ± 1.2 years. These evaluations detected a total of 112 colorectal adenomas, 31

Discussion

Few data exist on the colorectal phenotype of patients with LS. The present study evaluated colonoscopic findings in patients with LS confirmed by germline testing. These individuals were followed by serial colonoscopy, with an average interval between procedures of 1.7 years and an average of more than 9 years of follow-up, representing the longest follow-up study, to our knowledge, to date.

The overall cumulative risk of colorectal neoplasm in LS patients in the present study group was 43% by

Acknowledgments

The authors are indebted to Ms Linda Welch for technical support.

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Conflicts of interest The authors disclose no conflicts.

Funding Supported in part by the John G. Rangos, Sr. Charitable Foundation, The Clayton Fund, and NIH grants P50 CA 62924-17.

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