Declining detection rates for APC and biallelic MUTYH variants in polyposis patients, implications for DNA testing policy

Diantha Terlouw, Manon Suerink, Sunny S. Singh, Hans J. J. P. Gille, Frederik J. Hes, Alexandra M. J. Langers, Hans Morreau, Hans F. A. Vasen, Yvonne J. Vos, Tom van Wezel, Carli M. Tops, Sanne W. ten Broeke, Maartje Nielsen*

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    2 Citations (Scopus)

    Abstract

    This study aimed to determine the prevalence of APC-associated familial adenomatous polyposis (FAP) and MUTYH-associated polyposis (MAP) in a large cohort, taking into account factors as adenoma count and year of diagnosis. All application forms used to send patients in for APC and MUTYH variant analysis between 1992 and 2017 were collected (n = 2082). Using the data provided on the application form, the APC and biallelic MUTYH prevalence was determined and possible predictive factors were examined using multivariate multinomial logistic regression analysis in SPSS. The prevalence of disease causing variants in the APC gene significantly increases with adenoma count while MAP shows a peak prevalence in individuals with 50-99 adenomas. Logistic regression analysis shows significant odds ratios for adenoma count, age at diagnosis, and, interestingly, a decline in the chance of finding a variant in either gene over time. Moreover, in 22% (43/200) of patients with FAP-related extracolonic manifestations a variant was identified. The overall detection rates are above 10% for patients with >10 adenomas aged 20 adenomas aged T variant in the tumor or a first-degree relative with >10 adenomas. Therefore, APC and MUTYH testing in patients with >10 adenomas aged 20 adenomas aged

    Original languageEnglish
    Pages (from-to)222-230
    Number of pages9
    JournalEuropean Journal of Human Genetics
    Volume28
    Issue number2
    DOIs
    Publication statusPublished - Feb-2020

    Keywords

    • GERM-LINE MUTATIONS
    • ADENOMATOUS POLYPOSIS
    • COLORECTAL-CANCER
    • RISK
    • GENE
    • IDENTIFICATION
    • PREVALENCE
    • MOSAICISM
    • ONSET
    • FAP

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