Cancer risk in hereditary nonpolyposis colorectal cancer syndrome

later age of onset

Heather Hampel, Julie A Stephens, Eero Pukkala, Risto Sankila, Lauri A Aaltonen, Jukka-Pekka Mecklin, Albert de la Chapelle

    Research output: Contribution to journalArticleScientificpeer-review

    Abstract

    "Background & Aims: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine the penetrance in HNPCC using a comprehensive dataset from a geographically defined region. Methods: A combined dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by molecular screening comprising 88 probands and 373 mutation-positive family members was used. Statistical methods were modified survival analysis techniques. Results: In mutation-positive relatives (excluding probands), the median age at diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3-68.0 y). The lifetime risk for CRC was 68.7% (CI, 58.6%-78.9%) for men and 52.2% (CI, 37.6%-66.9%) for women. Considering only probands, the median age at diagnosis of CRC was 44.0 years (CI, 41.0 - 46.3 y). Median age of onset of EC was 62.0 years (CI, 55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of 54% (CI, 41.9%-66.1%). Conclusions: A markedly later age of onset for CRC at 61 y than previously reported (similar to 44 y) is suggested, resulting mainly from a more rigorous method of analysis in which all gene-positive individuals (both affected and unaffected with cancer) are considered. Lifetime cancer risks may be lower for CRC and endometrial cancer than presently assumed. If confirmed, these data suggest a need to alter counseling practices, and to consider HNPCC in older individuals than before."
    Original languageEnglish
    JournalGastroenterology
    Volume129
    Issue number2
    Pages (from-to)415-421
    Number of pages7
    ISSN0016-5085
    DOIs
    Publication statusPublished - 2005
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine

    Cite this

    Hampel, H., Stephens, J. A., Pukkala, E., Sankila, R., Aaltonen, L. A., Mecklin, J-P., & Chapelle, A. D. L. (2005). Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset. Gastroenterology, 129(2), 415-421. https://doi.org/10.1053/j.gastro.2005.05.011
    Hampel, Heather ; Stephens, Julie A ; Pukkala, Eero ; Sankila, Risto ; Aaltonen, Lauri A ; Mecklin, Jukka-Pekka ; Chapelle, Albert de la. / Cancer risk in hereditary nonpolyposis colorectal cancer syndrome : later age of onset. In: Gastroenterology. 2005 ; Vol. 129, No. 2. pp. 415-421.
    @article{a2cd6da8149e45dd83e7619cfb8eba67,
    title = "Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset",
    abstract = "{"}Background & Aims: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine the penetrance in HNPCC using a comprehensive dataset from a geographically defined region. Methods: A combined dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by molecular screening comprising 88 probands and 373 mutation-positive family members was used. Statistical methods were modified survival analysis techniques. Results: In mutation-positive relatives (excluding probands), the median age at diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3-68.0 y). The lifetime risk for CRC was 68.7{\%} (CI, 58.6{\%}-78.9{\%}) for men and 52.2{\%} (CI, 37.6{\%}-66.9{\%}) for women. Considering only probands, the median age at diagnosis of CRC was 44.0 years (CI, 41.0 - 46.3 y). Median age of onset of EC was 62.0 years (CI, 55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of 54{\%} (CI, 41.9{\%}-66.1{\%}). Conclusions: A markedly later age of onset for CRC at 61 y than previously reported (similar to 44 y) is suggested, resulting mainly from a more rigorous method of analysis in which all gene-positive individuals (both affected and unaffected with cancer) are considered. Lifetime cancer risks may be lower for CRC and endometrial cancer than presently assumed. If confirmed, these data suggest a need to alter counseling practices, and to consider HNPCC in older individuals than before.{"}",
    keywords = "311 Basic medicine",
    author = "Heather Hampel and Stephens, {Julie A} and Eero Pukkala and Risto Sankila and Aaltonen, {Lauri A} and Jukka-Pekka Mecklin and Chapelle, {Albert de la}",
    year = "2005",
    doi = "10.1053/j.gastro.2005.05.011",
    language = "English",
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    pages = "415--421",
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    number = "2",

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    Hampel, H, Stephens, JA, Pukkala, E, Sankila, R, Aaltonen, LA, Mecklin, J-P & Chapelle, ADL 2005, 'Cancer risk in hereditary nonpolyposis colorectal cancer syndrome: later age of onset', Gastroenterology, vol. 129, no. 2, pp. 415-421. https://doi.org/10.1053/j.gastro.2005.05.011

    Cancer risk in hereditary nonpolyposis colorectal cancer syndrome : later age of onset. / Hampel, Heather; Stephens, Julie A; Pukkala, Eero; Sankila, Risto; Aaltonen, Lauri A; Mecklin, Jukka-Pekka; Chapelle, Albert de la.

    In: Gastroenterology, Vol. 129, No. 2, 2005, p. 415-421.

    Research output: Contribution to journalArticleScientificpeer-review

    TY - JOUR

    T1 - Cancer risk in hereditary nonpolyposis colorectal cancer syndrome

    T2 - later age of onset

    AU - Hampel, Heather

    AU - Stephens, Julie A

    AU - Pukkala, Eero

    AU - Sankila, Risto

    AU - Aaltonen, Lauri A

    AU - Mecklin, Jukka-Pekka

    AU - Chapelle, Albert de la

    PY - 2005

    Y1 - 2005

    N2 - "Background & Aims: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine the penetrance in HNPCC using a comprehensive dataset from a geographically defined region. Methods: A combined dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by molecular screening comprising 88 probands and 373 mutation-positive family members was used. Statistical methods were modified survival analysis techniques. Results: In mutation-positive relatives (excluding probands), the median age at diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3-68.0 y). The lifetime risk for CRC was 68.7% (CI, 58.6%-78.9%) for men and 52.2% (CI, 37.6%-66.9%) for women. Considering only probands, the median age at diagnosis of CRC was 44.0 years (CI, 41.0 - 46.3 y). Median age of onset of EC was 62.0 years (CI, 55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of 54% (CI, 41.9%-66.1%). Conclusions: A markedly later age of onset for CRC at 61 y than previously reported (similar to 44 y) is suggested, resulting mainly from a more rigorous method of analysis in which all gene-positive individuals (both affected and unaffected with cancer) are considered. Lifetime cancer risks may be lower for CRC and endometrial cancer than presently assumed. If confirmed, these data suggest a need to alter counseling practices, and to consider HNPCC in older individuals than before."

    AB - "Background & Aims: Mutations in the mismatch repair genes cause hereditary nonpolyposis colorectal cancer (HNPCC) syndrome and convey high lifetime cancer risks for colorectal (CRC) and endometrial cancer. Currently, cancer risks for individuals with HNPCC are based on data from clinically ascertained families. The purpose of this study was to re-examine the penetrance in HNPCC using a comprehensive dataset from a geographically defined region. Methods: A combined dataset of 70 HNPCC families ascertained by traditional high-risk criteria and by molecular screening comprising 88 probands and 373 mutation-positive family members was used. Statistical methods were modified survival analysis techniques. Results: In mutation-positive relatives (excluding probands), the median age at diagnosis of CRC was 61.2 years (confidence interval [CI], 56.3-68.0 y). The lifetime risk for CRC was 68.7% (CI, 58.6%-78.9%) for men and 52.2% (CI, 37.6%-66.9%) for women. Considering only probands, the median age at diagnosis of CRC was 44.0 years (CI, 41.0 - 46.3 y). Median age of onset of EC was 62.0 years (CI, 55.9 y to an upper limit too high to calculate) with a lifetime cancer risk of 54% (CI, 41.9%-66.1%). Conclusions: A markedly later age of onset for CRC at 61 y than previously reported (similar to 44 y) is suggested, resulting mainly from a more rigorous method of analysis in which all gene-positive individuals (both affected and unaffected with cancer) are considered. Lifetime cancer risks may be lower for CRC and endometrial cancer than presently assumed. If confirmed, these data suggest a need to alter counseling practices, and to consider HNPCC in older individuals than before."

    KW - 311 Basic medicine

    U2 - 10.1053/j.gastro.2005.05.011

    DO - 10.1053/j.gastro.2005.05.011

    M3 - Article

    VL - 129

    SP - 415

    EP - 421

    JO - Gastroenterology

    JF - Gastroenterology

    SN - 0016-5085

    IS - 2

    ER -