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Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management

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Abstract

Hereditary forms of colorectal cancer, as is the case with virtually all forms of hereditary cancer, show extensive phenotypic and genotypic heterogeneity, a phenomenon discussed throughout this special issue of Familial Cancer. Clearly, the family physician, oncology specialist, genetic counselor, and cancer geneticist must know fully the complexity of hereditary cancer syndromes, their differential diagnosis, in order to establish a diagnosis, direct highly-targeted surveillance and management, and then be able to communicate effectively with the molecular geneticist so that an at-risk patient’s DNA can be tested in accord with the syndrome of concern. Thus, a family with features of the Lynch syndrome will merit microsatellite instability testing, consideration for immunohistochemistry evaluation, and mismatch repair gene testing, while, in contrast, a patient with FAP will require APC testing. However, other germline mutations, yet to be identified, may be important should testing for these mutations prove to be absent and, therein, unrewarding to the patient. Nevertheless, our position is that if the patient’s family history is consistent with one of these syndromes, but a mutation is not found in the family, we still recommend the same surveillance and management strategies for patients from families with an established cancer-causing germline mutation. Our purpose in this paper is to provide a concise coverage of the major hereditary colorectal cancer syndromes, to discuss genetic counseling, molecular genetic evaluation, highly targeted surveillance and management, so that cancer control can be maximized for these high hereditary cancer risk patients.

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Abbreviations

MMR:

mismatch repair

FAP:

familial adenomatous polyposis

AFAP:

attenuated familial adenomatous polyposis

HBCC:

hereditary breast and colorectal cancer

PJS:

Peutz–Jeghers syndrome

FJP:

familial juvenile polyposis

CD:

Cowden’s disease

BRRS:

Bannayan–Ruvalcaba–Riley syndrome

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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 National Institutes of Health through grant #1U01 CA 86389. 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.

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Authors and Affiliations

  1. Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, Nebraska, 68178, USA

    Henry T. Lynch, Jane F. Lynch & Thomas Attard

  2. Department of GI Medicine and Nutrition, University of Texas MD Anderson Cancer Center, Houston, Texas, USA

    Patrick M. Lynch

  3. Pediatric Gastroenterology, University of Nebraska Medical Center, Omaha, Nebraska, USA

    Thomas Attard

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  1. Henry T. Lynch
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  2. Jane F. Lynch
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Correspondence to Henry T. Lynch.

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Lynch, H.T., Lynch, J.F., Lynch, P.M. et al. Hereditary colorectal cancer syndromes: molecular genetics, genetic counseling, diagnosis and management. Familial Cancer 7, 27–39 (2008). https://doi.org/10.1007/s10689-007-9165-5

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