Original article—alimentary tractRapid Development of Colorectal Neoplasia in Patients With Lynch Syndrome
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.
References (16)
New developments in Lynch syndrome (hereditary nonpolyposis colorectal cancer) and mismatch repair gene testing
Gastroenterology
(2006)- et al.
Cumulative incidence of colorectal and extracolonic cancers in MLH1 and MSH2 mutation carriers of hereditary nonpolyposis colorectal cancer
J Gastrointest Surg
(1998) - et al.
Colorectal cancer screening: clinical guidelines and rationale
Gastroenterology
(1997) - et al.
Development of colorectal tumors in colonoscopic surveillance in Lynch syndrome
Gastroenterology
(2007) - et al.
Occurrence of colorectal adenomas in younger adults: an epidemiologic necropsy study
Clin Gastroenterol Hepatol
(2008) - et al.
Colorectal cancer screening and surveillance: clinical guidelines, evidence, and rationale
Gastroenterology
(1997) - et al.
Hereditary nonpolyposis colorectal cancer-morphologies, genes and mutations
Mutat Res
(1994) - et al.
Controlled 15 year trial on screening for colorectal cancer in families with hereditary nonpolyposis colorectal cancer
Gastroenterology
(2000)
Cited by (115)
Features of colorectal adenomas among young patients with Lynch syndrome according to path_MMR: Results from the PRED-IdF registry
2023, Digestive and Liver DiseaseSurvival outcomes associated with Lynch syndrome colorectal cancer and metachronous rate after subtotal/total versus segmental colectomy: Meta-analysis
2022, Surgery (United States)Citation Excerpt :There were no RCTs included in this study. Twelve studies (n = 1,469) reported on 5-year OS.2,17,20–22,28,29,31–34,36 Five-year OS was 89.5% (82.0–94.1%), P < .01; I2 = 89% (see Figure 2).
Hereditary Colorectal Cancer
2022, Hematology/Oncology Clinics of North AmericaLynch syndrome; towards more personalized management?
2022, Best Practice and Research: Clinical GastroenterologyCitation Excerpt :Individuals with LS are at risk of early-onset CRC and have a high cumulative lifetime risk of CRC that ranges according to MMR gene-specific risk between 15% and 70% at age 703−5. The prevalence of colonic polyps in patients with LS seems not higher than in the general population, but the microsatellite unstable pathway to CRC seems to be accelerated compared to most sporadic CRC cases with a reported dwell time as low as 3–3.5 years compared to 10–15 years in sporadic CRCs [14,15]. Ahadova et al. recently described a model based on three molecular pathways in colorectal carcinogenesis associated to LS: MMR deficiency commonly represents an early and possibly initiating event, and KRAS and APC mutations commonly occur after the onset of MMR deficiency, while CTNNB1 and TP53 mutations occurs in tumours lacking evidence of non-flat morphology polypoid growth [16].
Genetic testing for assessment of lynch syndrome in young patients with polyps
2021, Digestive and Liver DiseaseA step closer to a personalised approach for Lynch syndrome
2021, The Lancet Oncology
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.