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

Fam Cancer. 2021 Apr;20(2):111-116. doi: 10.1007/s10689-020-00198-x. Epub 2020 Aug 3.


Germline variants in the APC and MUTYH 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 of APC, monoallelic MUTYH and biallelic MUTYH germline variants in Ashkenazi Jewish (AJ) and Other Ancestry (OA) individuals with colorectal adenomas. We studied 7225 individuals with colorectal adenomas who had germline APC and MUTYH 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 of APC and MUTYH variants between AJ and OA, and examined APC p.I1307K and monoallelic MUTYH carrier phenotypes using logistic regression. Pathogenic APC variants occurred in 38/285 AJ (13%) and 1342/6940 OA (19%; P = 0.09); biallelic MUTYH 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 monoallelic MUTYH in 2/285 (1%) AJ and 133/6940 (2%) OA (P = 0.06). Monoallelic MUTYH 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 between APC 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 biallelic MUTYH variants, suggesting different genetic etiologies for polyposis in AJ compared to OA individuals. AJ ancestry assessment may be important in clinical evaluation for polyposis.

Keywords: Ancestry; Founder mutation testing strategy; MUTYH-associated polyposis; Polyposis in Ashkenazim.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoma / ethnology
  • Adenoma / genetics*
  • Cohort Studies
  • Colorectal Neoplasms / ethnology
  • Colorectal Neoplasms / genetics*
  • DNA Glycosylases / genetics*
  • Female
  • Gene Frequency
  • Genes, APC*
  • Genetic Testing
  • Germ-Line Mutation / genetics*
  • Humans
  • Jews / genetics*
  • Male
  • Middle Aged
  • Odds Ratio
  • Phenotype


  • DNA Glycosylases
  • mutY adenine glycosylase