Characterizing germline APC and MUTYH variants in Ashkenazi Jews compared to other individuals

AbstractGermline variants in theAPC andMUTYH genes contribute to colorectal cancer (CRC) and adenoma risk, though may occur with varying frequencies in individuals of different ancestries. The aim of this study was to evaluate the prevalence ofAPC, monoallelicMUTYH and biallelicMUTYH germline variants in Ashkenazi Jewish (AJ) and Other Ancestry (OA) individuals with colorectal adenomas. We studied 7225 individuals with colorectal adenomas who had germlineAPC andMUTYH testing at a commercial laboratory. Cross-sectional medical history data were extracted from provider-completed test requisition forms. We performed bivariate analysis to compare the frequency ofAPC andMUTYH variants between AJ and OA, and examinedAPC p.I1307K and monoallelicMUTYH carrier phenotypes using logistic regression. PathogenicAPC variants occurred in 38/285 AJ (13%) and 1342/6940 OA (19%;P = 0.09); biallelicMUTYH variants in 2/285 (1%) AJ and 399/6940 (6%) OA (P <  0.0001);APC p.I1307K in 35/285 (12%) AJ and 29/6940 (1%) OA (P <  0.0001); and monoallelicMUTYH in 2/285 (1%) AJ and 133/6940 (2%) OA (P = 0.06). MonoallelicMUTYH variants were significantly associated with having a personal history of CRC, regardless of ancestry (OR 1.78; 95% CI 1.21 –2.49;P <  0.01), but no significant association was found betweenAPC p.I1307K variants and personal history of CRC (OR 1.38; 95% CI 0.79 –2.44;P = 0.26). Ashkenazim with colorectal adenomas rarely have monoallelic or biallel...
Source: Familial Cancer - Category: Cancer & Oncology Source Type: research