title: Racial variation in frequency and phenotypes of APC and MUTYH mutations in 6,169 individuals undergoing genetic testing.
abstract: OBJECTIVE
  The aim of this study was to assess whether differences in frequency and phenotype of APC and MUTYH mutations exist among racially/ethnically diverse populations.
  
  
  METHODS
  We studied 6,169 individuals with a personal and/or family history of colorectal cancer (CRC) and polyps. APC testing involved full sequencing/large rearrangement analysis (FS/LRA); MUTYH involved "panel testing" (for Y165C, G382D mutations) or FS/LRA performed by Myriad Genetics, a commercial laboratory. Subjects were identified as Caucasian, Asian, African American (AA), or other. Statistical tests included χ(2), Fisher's exact test, analysis of variance, and z approximation.
  
  
  RESULTS
  Among participants, 17.5% had pathogenic APC mutations and 4.8% were biallelic MUTYH carriers. With regard to race/ethnicity, 18% were non-Caucasian, with >100 adenomas and younger ages at adenoma or CRC diagnosis (P < 0.0001) than Caucasians. The overall APC mutation rate was higher in Asians, AAs, and others as compared with Caucasians (25.2, 30.9, 24, and 15.5%, respectively; P < 0.0001) but was similar in all groups when adjusted for polyp burden. More MUTYH biallelic carriers were Caucasian or other than Asian or AA (5, 7, 2.7, and 0.3%, respectively; P < 0.0001). Among Caucasians, 5% were biallelic carriers identified by panel testing versus 2% identified by sequencing/large rearrangement analysis (LRA) (P = 0.002). Among non-Caucasians, 3% undergoing panel testing were biallelic carriers versus 10% identified by sequencing/LRA (P < 0.0002).
  
  
  CONCLUSIONS
  Non-Caucasians undergo genetic testing at more advanced stages of polyposis and/or are younger at CRC/polyp diagnosis. Restricted MUTYH analysis may miss significant numbers of biallelic carriers, particularly in non-Caucasians.
authors.affiliation: Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Inra
authors.affiliation: Center for Medical Decision Making, Erasmus Medical Center, Rotterdam, The Netherlands.
authors.forename: Ewout W
authors.initials: EW
authors.lastname: Steyerberg
authors.affiliation: Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Grover
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, USA.
authors.forename: Ashley
authors.initials: A
authors.lastname: McFarland
authors.affiliation: Division of Gastroenterology, Brigham and Women's Hospital, Boston, Massachusetts, USA.|Harvard Medical School, Boston, Massachusetts, USA.|Population Sciences Division, Dana-Farber Cancer Institute, Boston, Massachusetts, USA.
authors.forename: Sapna
authors.identifier: http://orcid.org/0000-0001-5487-7471
authors.initials: S
authors.lastname: Syngal
authors.affiliation: Division of Digestive and Liver Diseases, Columbia University Medical Center, New York, New York, USA.|Herbert Irving Comprehensive Cancer Center, New York, New York, USA.
authors.forename: Fay
authors.initials: F
authors.lastname: Kastrinos
mesh_terms: D011125:Adenomatous Polyposis Coli / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D000483:Alleles; D003430:Cross-Sectional Studies; D045647:DNA Glycosylases / Q000235:genetics*; D005260:Female; D005820:Genetic Testing; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D059645:Mutation Rate; D010641:Phenotype; D044469:Racial Groups / Q000235:genetics*; D047368:Tumor Burden
chemical_list: D045647:DNA Glycosylases; C061738:mutY adenine glycosylase