Colorectal cancer in HNPCC: cumulative lifetime incidence, survival and tumour distribution. A report of 121 families with proven mutations

Authors

  • E Barrow,

    Corresponding author
    1. Department of General Surgery, Manchester Royal Infirmary
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  • W Alduaij,

    1. Medical Genetics Research Group and Regional Genetics Service, St Mary’s Hospital, University of Manchester and Central Manchester and Manchester Children’s University Hospitals NHS Trust, Manchester, UK
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  • L Robinson,

    1. Medical Genetics Research Group and Regional Genetics Service, St Mary’s Hospital, University of Manchester and Central Manchester and Manchester Children’s University Hospitals NHS Trust, Manchester, UK
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  • A Shenton,

    1. Medical Genetics Research Group and Regional Genetics Service, St Mary’s Hospital, University of Manchester and Central Manchester and Manchester Children’s University Hospitals NHS Trust, Manchester, UK
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  • T Clancy,

    1. Medical Genetics Research Group and Regional Genetics Service, St Mary’s Hospital, University of Manchester and Central Manchester and Manchester Children’s University Hospitals NHS Trust, Manchester, UK
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  • F Lalloo,

    1. Medical Genetics Research Group and Regional Genetics Service, St Mary’s Hospital, University of Manchester and Central Manchester and Manchester Children’s University Hospitals NHS Trust, Manchester, UK
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  • J Hill,

    1. Department of General Surgery, Manchester Royal Infirmary
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  • DG Evans

    1. Medical Genetics Research Group and Regional Genetics Service, St Mary’s Hospital, University of Manchester and Central Manchester and Manchester Children’s University Hospitals NHS Trust, Manchester, UK
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  • *

    These authors have contributed equally to this work.

    The abstract for this article was submitted in December 2007 for presentation at The Association of Coloproctology of Great Britain and Ireland 2008 Annual Meeting, 30 June to 3 July 2008. It has since been accepted for oral presentation.

Emma Barrow, Research Office, Department of Clinical Genetics, St Mary’s Hospital, Hathersage Road, Manchester M13 0JH, UK.
Tel.: 0161 276 6080;
fax: 0161 276 6145;
e-mail: emma.barrow@doctors.org.uk

Abstract

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant condition caused by inactivating mutations of DNA mismatch repair (MMR) genes. An accurate estimation of colorectal cancer risk for mutation carriers is essential for counselling and rationalizing screening programmes. Families were referred on the basis of clinical criteria. Tumour immunohistochemistry and microsatellite testing were performed. Appropriate patients underwent sequencing of all relevant exons of the MMR genes. Proven and obligate mutation carriers and first-degree relatives (FDRs) with an HNPCC spectrum cancer were considered mutation carriers, as were a proportion of untested, unaffected FDRs based on the proportion of unaffected relatives testing positive in each age group. The cumulative lifetime risk was calculated by Kaplan–Meier analysis. Three hundred and forty-one colorectal cancers in 839 proven, obligate, or assumed mutation carriers were analysed. The cumulative risk to age 70 years for all mutation carriers combined was 50.4% (95% CI 47.8–52.9). The cumulative risk in males was 54.3% (95% CI 50.7–57.8), which was significantly higher than in females (log rank p = 0.02) who had a risk of 46.3% (95% CI 42.8–49.9). These penetrance estimates from HNPCC families attending high-risk clinics have been corrected for ascertainment bias and are appropriate risks for those referred to a high-risk clinic. Current colonoscopic screening guidelines are appropriate.

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