TY - JOUR
T1 - Declining detection rates for APC and biallelic MUTYH variants in polyposis patients, implications for DNA testing policy
AU - Terlouw, Diantha
AU - Suerink, Manon
AU - Singh, Sunny S.
AU - Gille, Hans J. J. P.
AU - Hes, Frederik J.
AU - Langers, Alexandra M. J.
AU - Morreau, Hans
AU - Vasen, Hans F. A.
AU - Vos, Yvonne J.
AU - van Wezel, Tom
AU - Tops, Carli. M.
AU - ten Broeke, Sanne W.
AU - Nielsen, Maartje
PY - 2020/2/1
Y1 - 2020/2/1
N2 - 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.
AB - 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85073810994&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31527860
U2 - https://doi.org/10.1038/s41431-019-0509-z
DO - https://doi.org/10.1038/s41431-019-0509-z
M3 - Article
C2 - 31527860
SN - 1018-4813
VL - 28
SP - 222
EP - 230
JO - European journal of human genetics
JF - European journal of human genetics
IS - 2
ER -