ArticleClinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association2011
Prevalence of alterations in DNA mismatch repair genes in patients with young-onset colorectal cancer.
Article in Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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42 citing papers in PubMed, 1 synthesis or guideline pooled it, 74 citations in OpenAlex.
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- Development of a whole-slide-level segmentation-based dMMR/pMMR deep learning detector for colorectal cancer.iScience · 2023Article
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- A Previously Unrecognized Molecular Landscape of Lynch Syndrome in the Mexican Population.International journal of molecular sciences · 2022Article
- Molecular Analysis of Colorectal Cancers Suggests a High Frequency of Lynch Syndrome in Indonesia.Cancers · 2021Article
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- Heterogeneous constitutional mismatch repair deficiency with MSH6 missense mutation clinically benefits from pembrolizumab and regorafenib combination therapy: a case report and literature review.Hereditary cancer in clinical practice · 2021Article
- Clinical-Grade Detection of Microsatellite Instability in Colorectal Tumors by Deep Learning.Gastroenterology · 2020Article
- Lynch-like syndrome is as frequent as Lynch syndrome in early-onset nonfamilial nonpolyposis colorectal cancer.International journal of cancer · 2019Article
- Investigation on the hereditary basis of colorectal cancers in an African population with frequent early onset cases.PloS one · 2019Article
- Molecular and presymptomatic analysis of a Moroccan Lynch syndrome family revealed a novel frameshift MLH1 germline mutation.The Turkish journal of gastroenterology : the official journal of Turkish Society of Gastroenterology · 2018Article
- Article
- Germline Genetic Features of Young Individuals With Colorectal Cancer.Gastroenterology · 2018Article
- Prevalence and clinicopathologic/molecular characteristics of mismatch repair-deficient colorectal cancer in the under-50-year-old Japanese population.Surgery today · 2017Article
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10 authors at 5 institutions in 2 countries.
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Abstract
BACKGROUND &
aimsDirect germline analysis could be used to screen high-risk patients for mutations in DNA mismatch repair genes associated with Lynch Syndrome. We examined the prevalence of mutations in MLH1, MSH2, and MSH6 in a population-based sample of patients with young-onset (age <50 years) colorectal cancer (CRC).
methodsYoung-onset CRC cases were randomly selected from 3 Colon Cancer Family Registry sites. DNA was extracted from peripheral blood leukocytes; MLH1, MSH2, and MSH6 were sequenced, and duplication and deletion analyses was performed for MLH1 and MSH2. Results were reported as deleterious or suspected deleterious, likely neutral, variant of uncertain significance, or no alteration detected. Germline data were compared to Amsterdam II criteria (ACII) and immunohistochemistry results in secondary analyses.
resultsAmong 195 subjects, 11 had deleterious/suspected deleterious mutations (5.6%; 95% confidence interval [CI], 2.8%-9.9%), 12 had likely neutral alterations (6.2%; 95% CI, 3.2%-10.5%), 14 had variants of uncertain significance (7.2%; 95% CI, 4.0%-11.8%), 2 had a likely neutral alteration and a variant of uncertain significance (1.0%; 95% CI, 0.1%-3.7%), and 156 had no alteration detected (80.0%; 95% CI, 73.7%-85.4%). Sensitivity, specificity, and positive and negative predictive values for detecting deleterious/suspected deleterious mutations, based on ACII, were 36.4% (4/11), 96.7% (178/184), 40.0% (4/10), and 96.2% (178/185), respectively; based on immunohistochemistry these values were 85.7% (6/7), 91.9% (136/148), 33.3% (6/18), and 99.3% (136/137), respectively.
conclusionsIn a population-based sample of young-onset CRC cases, germline mutations in MLH1, MSH, and/or MSH6 were more prevalent than reported for CRC patients overall. Because only about 5% of young-onset CRC cases had confirmed deleterious or suspected deleterious mutations, further comparative effectiveness research is needed to determine the most appropriate screening strategy for Lynch Syndrome in this high-risk group.
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