Abstract
Lynch syndrome is the most common form of hereditary colorectal cancer (CRC). This review covers the cardinal features of Lynch syndrome with particular emphasis upon its diagnostic criteria, molecular genetics, natural history, genetic counseling, surveillance and management. Considerable attention has been given to the etiologic role of mismatch repair (MMR) genes as well as low penetrance alleles and modifier genes. The American founder mutation, a deletion of exons 1–6 of MSH2, is discussed in some detail, owing to its high frequency in the US (19 000–30 000 carriers). Genetic counseling is essential prior to patients’ undergoing DNA testing and again when receiving their test results. Families with a lower incidence of CRC and extracolonic cancers, in the face of being positive for Amsterdam I criteria but who do not have MMR deficiency by tumor testing, are probably not Lynch syndrome, and thereby should preferably be designated as familial CRC of undetermined type. Patients who are either noncompliant or poorly compliant with colonoscopy, and who are MMR mutation positive, may be candidates for prophylactic colectomy, while MMR mutation-positive women who are noncompliant with gynecologic surveillance may be candidates for prophylactic hysterectomy and bilateral salpingo-oophorectomy.
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Acknowledgements
This article was supported by revenue from Nebraska cigarette taxes awarded to Creighton University by the Nebraska Department of Health and Human Services. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the State of Nebraska or the Nebraska Department of Health and Human Services. Support was also given by the Jacqueline Seroussi Memorial Foundation for Cancer Research, by the National Institutes of Health through Grant nos. 1U01 CA 86389-04, P30 CA 16058 and R01 CA 67941. Dr Henry Lynch's work is partially funded through the Charles F and Mary C Heider Chair in Cancer Research, which he holds at Creighton University. Dr de la Chapelle's work is partially funded by the State of Ohio Biomedical and Technology Transfer Commission. The views expressed in this article are those of the authors and do not necessarily reflect the views of the State of Ohio Biomedical and Technology Transfer Commission. Dr Boland is funded by a Grant from the National Cancer Institute, NIH, R01-CA 72851, and an endowed chair from the Baylor Research Institute.
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Lynch, H., Boland, C., Gong, G. et al. Phenotypic and genotypic heterogeneity in the Lynch syndrome: diagnostic, surveillance and management implications. Eur J Hum Genet 14, 390–402 (2006). https://doi.org/10.1038/sj.ejhg.5201584
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DOI: https://doi.org/10.1038/sj.ejhg.5201584
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