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Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition

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Abstract

Development of multiple colorectal cancers (CRCs), synchronously or metachronously, is associated with hereditary predisposition for cancer and accurate risk estimates of multiple tumour development are relevant to recommend rational surveillance programs. A cross-sectional study design was used to estimate the risks of synchronous CRC (SCRC) and metachronous CRC (MCRC) based on data from the National Danish Hereditary Nonpolyposis Register. In total, 7100 individuals from families within the subgroups Lynch syndrome, familial CRC (FCC) and moderate risk were used with estimates relative to a non-hereditary population control cohort. SCRC was diagnosed in 7.4% of the Lynch syndrome cases, in 4.2% of FCC cases and 2.5% of the moderate risk cases, which translated to relative risks of 1.9–5.6. The risk of MCRC was distinctively linked to Lynch syndrome with a life-time risk up to 70% and an incidence rate ratio of 5.0. The risk of SCRC was significantly increased in all subgroups of FCC and hereditary CRC, whereas the risk of MCRC was specifically linked to Lynch syndrome. These observations suggest that individuals with FCC or hereditary CRC should be carefully screened for second primary CRC at the time of diagnosis, whereas intensified surveillance for second primary CRC is motivated in Lynch syndrome with lower-intensity programs in families with yet unidentified genetic causes.

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Acknowledgements

Financial support was granted from the Danish Cancer Society (Grant No. R90-A6150) and from the Swedish Cancer Society (Grant No. 2014/442). We would also like to thank all clinicians who have contributed with data to the Danish HNPCC Register.

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Authors and Affiliations

  1. The Danish HNPCC Register, Clinical Research Centre, Copenhagen University Hospital, Hvidovre, Kettegaard Allé 30, DK2650, Hvidovre, Denmark

    Lars J. Lindberg, Wia Wegen-Haitsma, Steen Ladelund, Lars Smith-Hansen, Christina Therkildsen & Mef Nilbert

  2. Department of Surgical Gastroenterology, Aalborg University Hospital, Ålborg, Denmark

    Inge Bernstein

  3. Institute of Clinical Sciences, Division of Oncology and Pathology, Lund University, Lund, Sweden

    Mef Nilbert

  4. The Danish Cancer Society Research Center, Copenhagen, Denmark

    Mef Nilbert

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  1. Lars J. Lindberg
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Correspondence to Lars J. Lindberg.

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Lindberg, L.J., Wegen-Haitsma, W., Ladelund, S. et al. Risk of multiple colorectal cancer development depends on age and subgroup in individuals with hereditary predisposition. Familial Cancer 18, 183–191 (2019). https://doi.org/10.1007/s10689-018-0109-z

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