Journal of the National Cancer Institute Advance Access published online on February 12, 2008
JNCI Journal of the National Cancer Institute, doi:10.1093/jnci/djm291
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© The Author 2008. Published by Oxford University Press.
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The Frequency of Muir-Torre Syndrome Among Lynch Syndrome Families
Affiliations of authors: Division of Gastroenterology, Hepatology, and Nutrition (CDS), Department of Pathology (WLF), and the Human Cancer Genetics Program, Comprehensive Cancer Center (HH, IC, JAW, AdlC), The Ohio State University-Columbus, OH
Correspondence to: Albert de la Chapelle, MD, PhD, Human Cancer Genetics Program, 646 Tzagournis Medical Research Facility, 420 West 12th Ave, Columbus, OH 43210 (e-mail: albert.delachapelle{at}osumc.edu).
Lynch syndrome is the predisposition to visceral malignancies that are associated with deleterious germline mutations in DNA mismatch repair genes, including MLH1, MSH2, MSH6, and PMS2. Muir-Torre syndrome is a variant of Lynch syndrome that includes a predisposition to certain skin tumors. We determined the frequency of Muir-Torre syndrome among 50 Lynch syndrome families that were ascertained from a population-based series of cancer patients who were newly diagnosed with colorectal or endometrial carcinoma. Histories of Muir-Torre syndrome–associated skin tumors were documented during counseling of family members. Muir-Torre syndrome was observed in 14 (28%) of 50 families and in 14 (9.2%) of 152 individuals with Lynch syndrome. Four (44%) of nine families with MLH1 mutations had a member with Muir-Torre syndrome compared with 10 (42%) of 24 families with MSH2 mutations (P = .302). Families who carried the c.942+3A>T MSH2 gene mutation had a higher frequency of Muir-Torre syndrome than families who carried other mutations in the MSH2 gene (75% vs 25%; P = .026). Muir-Torre syndrome was not found in families with mutations in the MSH6 or PMS2 genes. Our results suggest that Muir-Torre syndrome is simply a variant of Lynch syndrome. Screening for Muir-Torre syndrome–associated skin lesions among patients with Lynch syndrome is recommended.
| CONTEXT AND CAVEATS Prior knowledge Some individuals with Lynch syndrome—an inherited predisposition to develop colorectal and other specific cancers—also have a tendency to develop certain kinds of skin tumors (ie, Muir-Torre syndrome). Cancerous lesions associated with both syndromes are characterized by inherited deleterious mutations in DNA mismatch repair (MMR) genes, including MSH2. Study design A cohort study to examine the frequency of Muir-Torre syndrome–related skin tumors among 50 Lynch syndrome families (confirmed by MMR gene mutation analysis) who were ascertained from a population-based series of patients newly diagnosed with colorectal or endometrial cancer. Contribution Muir-Torre syndrome was observed in 28% of the 50 families and in 9.2% of the 152 individuals with Lynch syndrome. The frequency of Muir-Torre syndrome was 75% among families who carried a specific deleterious mutation in the MSH2 gene vs 25% among families who carried other mutations in this gene. Limitations There was a preponderance of the Muir-Torre syndrome–associated deleterious MSH2 gene mutation in the study cohort. Histories of skin lesions may have been subject to recall bias. Implications Patients with Lynch syndrome should be screened for Muir-Torre syndrome–associated skin lesions.
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This publication was prepared under a grant from the State of Ohio Biomedical Research and Technology Transfer Commission. The content reflects the views of the Grantee and does not necessarily reflect the views of the State of Ohio Biomedical Research and Technology Transfer Commission. Ms Hampel had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Manuscript received August 15, 2007; revised November 26, 2007; accepted November 28, 2007.
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