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 <60 and >20 adenomas aged <70. Patients with variants outside these criteria had FAP-related extracolonic manifestations, colorectal cancer aged <40, somatic KRAS c.34G > T variant in the tumor or a first-degree relative with >10 adenomas. Therefore, APC and MUTYH testing in patients with >10 adenomas aged <60 and with >20 adenomas aged <70 is advised. Almost all FAP and MAP patients not meeting these criteria showed other characteristics that can be used as an indication to prompt genetic testing.
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Funding for assistance in English writing was provided by the Department Of Clinical Genetics, LUMC.
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DT had full access to all the data in the study and takes responsibility for the integrity of the data and accuracy of the data analysis. Study concept and design: SWtB, MN. Acquisition of data: CMT, SSS, and SWtB. Analysis and interpretation of the data: DT, MS, SWtB, MN, and SSS. Critical revision of the manuscript for important intellectual content: all authors. Statistical analysis: DT, SWtB, and MN.
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Terlouw, D., Suerink, M., Singh, S.S. et al. Declining detection rates for APC and biallelic MUTYH variants in polyposis patients, implications for DNA testing policy. Eur J Hum Genet 28, 222–230 (2020). https://doi.org/10.1038/s41431-019-0509-z
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DOI: https://doi.org/10.1038/s41431-019-0509-z
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